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Background Particulate matter (PM), a major component of ambient air pollution, accounts for a substantial burden of diseases and fatality worldwide. Maternal exposure to PM during pregnancy is particularly harmful to children’s health since this is a phase of rapid human growth and development. Method In this review, we synthesize the scientific evidence on adverse health outcomes in children following prenatal exposure to the smallest toxic components, fine (PM2.5) and ultrafine (PM0.1) PM. We highlight the established and emerging findings from epidemiologic studies and experimental models. Results Maternal exposure to fine and ultrafine PM directly and indirectly yields numerous adverse birth outcomes and impacts on children’s respiratory systems, immune status, brain development, and cardiometabolic health. The biological mechanisms underlying adverse effects include direct placental translocation of ultrafine particles, placental and systemic maternal oxidative stress and inflammation elicited by both fine and ultrafine PM, epigenetic changes, and potential endocrine effects that influence long-term health. Conclusion Policies to reduce maternal exposure and health consequences in children should be a high priority. PM2.5 levels are regulated, yet it is recognized that minority and low socioeconomic status groups experience disproportionate exposures. Moreover, PM0.1 levels are not routinely measured or currently regulated. Consequently, preventive strategies that inform neighborhood/regional planning and clinical/nutritional recommendations are needed to mitigate maternal exposure and ultimately protect children’s health.
Natalie M. Johnson; Aline Rodrigues Hoffmann; Jonathan C. Behlen; Carmen Lau; Drew Pendleton; Navada Harvey; Ross Shore; Yixin Li; Jingshu Chen; Yanan Tian; Renyi Zhang. Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter. Environmental Health and Preventive Medicine 2021, 26, 1 -29.
AMA StyleNatalie M. Johnson, Aline Rodrigues Hoffmann, Jonathan C. Behlen, Carmen Lau, Drew Pendleton, Navada Harvey, Ross Shore, Yixin Li, Jingshu Chen, Yanan Tian, Renyi Zhang. Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter. Environmental Health and Preventive Medicine. 2021; 26 (1):1-29.
Chicago/Turabian StyleNatalie M. Johnson; Aline Rodrigues Hoffmann; Jonathan C. Behlen; Carmen Lau; Drew Pendleton; Navada Harvey; Ross Shore; Yixin Li; Jingshu Chen; Yanan Tian; Renyi Zhang. 2021. "Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter." Environmental Health and Preventive Medicine 26, no. 1: 1-29.
Growth hormone secretagogue receptor (GHS-R) is widely known to regulate food intake and adiposity, but its role in glucose homeostasis is unclear. In this study, we investigated the expression of GHS-R in mouse pancreatic islets and its role in glycemic regulation. We used Ghsr-IRES-tauGFP mice, with Green Fluorescent Protein (GFP) as a surrogate for GHS-R, to demonstrate the GFP co-localization with insulin and glucagon expression in pancreatic islets, confirming GHS-R expression in β and α cells. We then generated β-cell-specific GHSR-deleted mice with MIP-Cre/ERT and validated that GHS-R suppression was restricted to the pancreatic islets. MIP-Cre/ERT;Ghsrf/f mice showed normal energy homeostasis with similar body weight, body composition, and indirect calorimetry profile. Interestingly, MIP-Cre/ERT;Ghsrf/f mice exhibited an impressive phenotype in glucose homeostasis. Compared to controls, MIP-Cre/ERT;Ghsrf/f mice showed lower fasting blood glucose and insulin; reduced first-phase insulin secretion during a glucose tolerance test (GTT) and glucose-stimulated insulin secretion (GSIS) test in vivo. The isolated pancreatic islets of MIP-Cre/ERT;Ghsrf/f mice also showed reduced insulin secretion during GSIS ex vivo. Further, MIP-Cre/ERT;Ghsrf/f mice exhibited improved insulin sensitivity during insulin tolerance tests (ITT). Overall, our results confirmed GHS-R expression in pancreatic β and α cells; GHS-R cell-autonomously regulated GSIS and modulated systemic insulin sensitivity. In conclusion, β cell GHS-R was an important regulator of glucose homeostasis, and GHS-R antagonists may have therapeutic potential for Type 2 Diabetes.
Geetali Pradhan; Chia-Shan Wu; Daniel Villarreal; Jong Lee; Hye Han; Akhilesh Gaharwar; Yanan Tian; Wenxian Fu; Shaodong Guo; Roy Smith; Yuxiang Sun. β Cell GHS-R Regulates Insulin Secretion and Sensitivity. International Journal of Molecular Sciences 2021, 22, 3950 .
AMA StyleGeetali Pradhan, Chia-Shan Wu, Daniel Villarreal, Jong Lee, Hye Han, Akhilesh Gaharwar, Yanan Tian, Wenxian Fu, Shaodong Guo, Roy Smith, Yuxiang Sun. β Cell GHS-R Regulates Insulin Secretion and Sensitivity. International Journal of Molecular Sciences. 2021; 22 (8):3950.
Chicago/Turabian StyleGeetali Pradhan; Chia-Shan Wu; Daniel Villarreal; Jong Lee; Hye Han; Akhilesh Gaharwar; Yanan Tian; Wenxian Fu; Shaodong Guo; Roy Smith; Yuxiang Sun. 2021. "β Cell GHS-R Regulates Insulin Secretion and Sensitivity." International Journal of Molecular Sciences 22, no. 8: 3950.
Prior exposures to chemicals/agents may alter epigenome in such a way that subsequent exposure to the same or different xenobiotic would produce different responses. Understanding the mechanism for this “priming” effect is of clinical significance in avoiding adverse drug-drug interactions. Here we reported a dramatic priming effect of dimethyl sulfoxide (DMSO) on pregnane X receptor (PXR)-mediated gene regulations and analyzed the underpinning epigenetic mechanism. We showed that DMSO (1.25–2.5 %) pretreatment has a profound effect in enhancing the expression of PXR target genes. This priming effect persisted up to 48 h. Mechanistically, DMSO pretreatment reduced H4K12 acetylation and therefore enhanced the subsequent rifampicin stimulated histone H4R3 methylation on the regulatory region of PXR target gene CYP3A4. We showed that protein arginine methyltransferase 1 (PRMT1), which methylates H4R3, was important for priming by DMSO. Inhibition of methyltransferase by the pharmacological inhibitor adenosine dialehyde (AdoX), or RNAi knockdown of PRMT1, abolished the DMSO priming effects. On the other hand, Trichostation A (TSA) pretreatment, which increases histone acetylation and therefore suppresses H4R3 methylation, also abolished the DMSO priming effects. Based on the above observation, we proposed a model of sequential order of histone methylation and acetylation on the transcription “relay”.
Ying Xie; Sui Ke; Jingshu Chen; Nengtai Ouyang; Yanan Tian. Epigenetic sensitization of pregnane X receptor-regulated gene expression by dimethyl sulfoxide. Toxicology Letters 2019, 321, 131 -137.
AMA StyleYing Xie, Sui Ke, Jingshu Chen, Nengtai Ouyang, Yanan Tian. Epigenetic sensitization of pregnane X receptor-regulated gene expression by dimethyl sulfoxide. Toxicology Letters. 2019; 321 ():131-137.
Chicago/Turabian StyleYing Xie; Sui Ke; Jingshu Chen; Nengtai Ouyang; Yanan Tian. 2019. "Epigenetic sensitization of pregnane X receptor-regulated gene expression by dimethyl sulfoxide." Toxicology Letters 321, no. : 131-137.
T-2 toxin is a mycotoxin generated by Fusarium species which has been shown to be highly toxic to human and animals. T-2 toxin induces apoptosis in various tissues/organs. Apoptosis and autophagy are two closely interconnected processes, which are important for maintaining physiological homeostasis as well as pathogenesis. Here, for the first time, we demonstrated that T-2 toxins induce autophagy in human liver cells (L02). We demonstrated that T-2 toxin induce acidic vesicular organelles formation, concomitant with the alterations in p62/SQSTM1 and LC3-phosphatidylethanolamine conjugate (LC3-II) and the enhancement of the autophagic flux. Using mRFP-GFP-LC3 by lentiviral transduction, we showed T-2 toxin-mediated lysosomal fusion and the formation of autophagosomes in L02 cells. The formation of autophagosomes was further confirmed by transmission electron microcopy. While T-2 toxin induced both autophagy and apoptosis, autophagy appears to be a leading event in the response to T-2 toxin treatment, reflecting its protective role in cells against cellular damage. Activating autophagy by rapamycin (RAPA) inhibited apoptosis, while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis, suggesting the crosstalk between autophagy and apoptosis. Taken together, these results indicate that autophagy plays a role in protecting cells from T-2 toxin-induced apoptosis suggesting that autophagy may be manipulated for the alleviation of toxic responses induced by T-2 toxin.
Jing Wu; Yu Zhou; Zhihang Yuan; Jine Yi; Jingshu Chen; Naidong Wang; Yanan Tian. Autophagy and Apoptosis Interact to Modulate T-2 Toxin-Induced Toxicity in Liver Cells. Toxins 2019, 11, 45 .
AMA StyleJing Wu, Yu Zhou, Zhihang Yuan, Jine Yi, Jingshu Chen, Naidong Wang, Yanan Tian. Autophagy and Apoptosis Interact to Modulate T-2 Toxin-Induced Toxicity in Liver Cells. Toxins. 2019; 11 (1):45.
Chicago/Turabian StyleJing Wu; Yu Zhou; Zhihang Yuan; Jine Yi; Jingshu Chen; Naidong Wang; Yanan Tian. 2019. "Autophagy and Apoptosis Interact to Modulate T-2 Toxin-Induced Toxicity in Liver Cells." Toxins 11, no. 1: 45.
T-2 toxin produced by fungi of Fusarium genus is highly toxic to human and animals and has been shown to induce apoptosis in various organs/tissues. Apoptosis and autophagy are interconnected processes and these interactions are important for cellular homeostasis as well as pathogenesis. In this study, we report for the first time that T-2 toxin induced autophagy in human liver cells (L02). We showed that T-2 toxin induced the formation of acidic vesicular organelles, concordant with the time and dose-dependent alterations in LC3-phosphatidylethanolamine conjugate (LC3-II) LC3-I/II and p62/SQSTM1 suggesting an enhanced autophagic flux. The T-2 toxin-induced formation of autophagosome and lysosomal fusion was observed by expressing mRFP-GFP-LC3 in L02 cells by lentiviral transduction, and autophagosome was observed by transmission electron microcopy. We found that while T-2 toxin activated both apoptosis and autophagy, activation of autophagy appears to be a leading event reflecting the protective mechanism of cells against the insults by T-2 toxin. Activating autophagy by rapamycin (RAPA) inhibited the apoptosis while suppressing autophagy by chloroquine greatly enhanced the T-2 toxin-induced apoptosis suggesting the crosstalk of autophagy and apoptosis. In summary, our study showed that activation of autophagy protects liver cells from T-2 toxin-induced apoptosis suggesting autophagy may be targeted for prevention of the T-2 toxin-induced toxicity in human and animals.
Jing Wu; Yu Zhou; Zhihang Yuan; Jine Yi; Jingshu Chen; Naidong Wang; Yannan Tian. Crosstalk between Autophagy and Apoptosis Modulates T-2 Toxin-Induced Toxicity in Liver Cells. 2018, 1 .
AMA StyleJing Wu, Yu Zhou, Zhihang Yuan, Jine Yi, Jingshu Chen, Naidong Wang, Yannan Tian. Crosstalk between Autophagy and Apoptosis Modulates T-2 Toxin-Induced Toxicity in Liver Cells. . 2018; ():1.
Chicago/Turabian StyleJing Wu; Yu Zhou; Zhihang Yuan; Jine Yi; Jingshu Chen; Naidong Wang; Yannan Tian. 2018. "Crosstalk between Autophagy and Apoptosis Modulates T-2 Toxin-Induced Toxicity in Liver Cells." , no. : 1.
Exposure to certain environmental chemicals in human and animals has been found to cause cellular damage of the pancreatic β cells which will lead to the development of type 2 diabetes mellitus (T2DM). Although the mechanisms for the chemical-induced β cell damage were unclear and likely to be complex, one recurring finding is that these chemicals induce oxidative stress leading to the generation of excessive reactive oxygen species (ROS) which induce damage to the β cell. To identify potential diabetogenic environmental chemicals, we isolated pancreatic islet cells from C57BL/6 mice and cultured islet cells in 96-well cell culture plates; then, the islet cells were dosed with chemicals and the ROS generation was detected by 2',7'-dichlorofluorescein (DCFH-DA) fluorescent dye. Using this method, we found that bisphenol A (BPA), Benzo[a]pyrene (BaP), and polychlorinated biphenyls (PCBs), could induce high levels of ROS, suggesting that they may potentially induce damage in islet cells. This method should be useful for screening diabetogenic xenobiotics. In addition, the cultured islet cells may also be adapted for in vitro analysis of chemical-induced toxicity in pancreatic cells.
Jingshu Chen; Lei Zhong; Jing Wu; Sui Ke; Benjamin Morpurgo; Andrei Golovko; Nengtai Ouyang; Yuxiang Sun; Shaodong Guo; Yanan Tian. A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals. Journal of Visualized Experiments 2018, e57327 -e57327.
AMA StyleJingshu Chen, Lei Zhong, Jing Wu, Sui Ke, Benjamin Morpurgo, Andrei Golovko, Nengtai Ouyang, Yuxiang Sun, Shaodong Guo, Yanan Tian. A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals. Journal of Visualized Experiments. 2018; (136):e57327-e57327.
Chicago/Turabian StyleJingshu Chen; Lei Zhong; Jing Wu; Sui Ke; Benjamin Morpurgo; Andrei Golovko; Nengtai Ouyang; Yuxiang Sun; Shaodong Guo; Yanan Tian. 2018. "A Murine Pancreatic Islet Cell-based Screening for Diabetogenic Environmental Chemicals." Journal of Visualized Experiments , no. 136: e57327-e57327.
The metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long noncoding RNA and its overexpression is associated with the development of many types of malignancy. MALAT1 null mice show no overt phenotype. However, in transcriptome analysis of MALAT1 null mice we found significant upregulation of nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) regulated antioxidant genes including Nqo1 and Cat with significant reduction in reactive oxygen species (ROS) and greatly reduced ROS-generated protein carbonylation in hepatocyte and islets. We performed lncRNA pulldown assay using biotinylated antisense oligonucleotides against MALAT1 and found MALAT1 interacted with Nrf2, suggesting Nrf2 is transcriptionally regulated by MALAT1. Exposure to excessive ROS has been shown to cause insulin resistance through activation of c-Jun N-terminal kinase (JNK) which leads to inhibition of insulin receptor substrate 1 (IRS-1) and insulin-induced phosphorylation of serine/threonine kinase Akt. We found MALAT1 ablation suppressed JNK activity with concomitant insulin-induced activation of IRS-1 and phosphorylation of Akt suggesting MALAT1 regulated insulin responses. MALAT1 null mice exhibited sensitized insulin-signaling response to fast-refeeding and glucose/insulin challenges and significantly increased insulin secretion in response to glucose challenge in isolated MALAT1 null islets, suggesting an increased insulin sensitivity. In summary, we demonstrate that MALAT1 plays an important role in regulating insulin sensitivity and has the potential as a therapeutic target for the treatment of diabetes as well as other diseases caused by excessive exposure to ROS.
Jingshu Chen; Sui Ke; Lei Zhong; Jing Wu; Alexander Tseng; Benjamin Morpurgo; Andrei Golovko; Gang Wang; James Cai; Xi Ma; Defa Li; Yanan Tian. Long noncoding RNA MALAT1 regulates generation of reactive oxygen species and the insulin responses in male mice. Biochemical Pharmacology 2018, 152, 94 -103.
AMA StyleJingshu Chen, Sui Ke, Lei Zhong, Jing Wu, Alexander Tseng, Benjamin Morpurgo, Andrei Golovko, Gang Wang, James Cai, Xi Ma, Defa Li, Yanan Tian. Long noncoding RNA MALAT1 regulates generation of reactive oxygen species and the insulin responses in male mice. Biochemical Pharmacology. 2018; 152 ():94-103.
Chicago/Turabian StyleJingshu Chen; Sui Ke; Lei Zhong; Jing Wu; Alexander Tseng; Benjamin Morpurgo; Andrei Golovko; Gang Wang; James Cai; Xi Ma; Defa Li; Yanan Tian. 2018. "Long noncoding RNA MALAT1 regulates generation of reactive oxygen species and the insulin responses in male mice." Biochemical Pharmacology 152, no. : 94-103.
Cytochrome P450 (CYP) enzymes belong to a superfamily of monooxygenases which are phase I enzymes responsible for the first pass metabolism of about 90% of drugs in animals. However, these enzymes are often polymorphic and metabolism of the same drug in different species or different individuals is influenced by genetic and non-genetic factors. Bactrian camels are capable of survival in harsh living environments, being able to consume diets that are often toxic to other mammals and can tolerate extreme water and food deprivation. The aim of this study was to investigate whether the Bactrian camel’s special metabolic pathways and unique detoxification capabilities are attributable to particularities of the CYP gene family. The Bactrian camel’s whole genome sequencing data were systemically analyzed and annotated, and then, CYP gene family was searched from the whole protein database and compared with CYP gene families of cattle, horse, chicken, and human. The total of 63 CYP gene copies were found in Bactrian camel’s whole genome and were classified into 17 families and 38 subfamilies. Among them, 9 multi-gene families were found, and CYP2, CYP3, and CPY4 have 27, 6, and 7 subfamilies, accounting for 43, 10, and 11% in camel CYP gene, respectively. In comparison with cattle, chicken, horse, and human, the distribution of CYP gene subfamilies in camel is different, with more CYP2J and CYP3A copies in the Bactrian camel, which may contribute to the Bactrian camel’s specific biological characteristics and metabolic pathways. Comparing to the cow, horse, chicken, and human CYP genes, the distribution of CYP gene subfamilies is distinct in the Bactrian camel. The higher copy number of CYP2J gene and CYP3A gene in Bactrian camel may be the important factors contributing to the distinct biological characteristics and metabolic pathways of Bactrian camels for adaptation to the harsh environments.
Surong Hasi; Jirimutu Yao; Siriguleng Yu; Yanan Tian. Diversity and distribution of CYP gene family in Bactrian camel. Functional & Integrative Genomics 2017, 18, 23 -29.
AMA StyleSurong Hasi, Jirimutu Yao, Siriguleng Yu, Yanan Tian. Diversity and distribution of CYP gene family in Bactrian camel. Functional & Integrative Genomics. 2017; 18 (1):23-29.
Chicago/Turabian StyleSurong Hasi; Jirimutu Yao; Siriguleng Yu; Yanan Tian. 2017. "Diversity and distribution of CYP gene family in Bactrian camel." Functional & Integrative Genomics 18, no. 1: 23-29.
Pregnane X receptor (PXR) plays an important role in protecting cells from mutagenic DNA damages induced by endogenous and exogenous toxicants. This protective function is often attributed to the PXR-regulated metabolic detoxification. Here we report a novel potential mechanism that PXR reduces benzo-[α]-pyrene(BaP)-induced DNA damage through inhibiting the transcriptional activity of aryl hydrocarbon receptor (AhR) which plays a pivotal role in the bioactivation of BaP. We have utilized three well-characterized cell lines, i.e. Hepa1c1c7, AhR +/+; Bpr lacks AhR obligatory partner ARNT; Tao, lacks AhR, to analyze pivotal role of AhR/ARNT complex in mediating the BaP-induced DNA damages using comet assay (single-cell gel electrophoresis). We found that PXR activation could significantly inhibit BaP-induced DNA damage in the HepG2 cells as well as mouse hepatocytes. Using PXR-null and wild type mouse hepatocytes we showed that PXR activation by pregnenolone 16α-carbonitrile (PCN) significantly inhibited BaP-induced DNA damage and this protective effect was abolished in PXR-null hepatocytes. Mechanistically, PXR activation inhibited expression of AhR-target genes for CYP1A1, CYP1B1 and CYP1A2 that are required for BaP biotransformation in cultured liver cells, or in the livers of C57BL/6J mice. Using an AhR-responsive reporter assay as well as chromatin immunoprecipitation assay we found that PXR activation transcriptionally represses AhR-regulated gene expression. Furthermore, we found that PXR directly bound AhR at its DNA-binding domain, and this association may play a role in preventing of the AhR from binding to its target genes as shown in the ChIP assay. Taken together, our study has revealed a novel mechanism by which PXR protects liver cells from BaP-induced DNA damage through inhibiting the BaP biotransformation.
Hongmei Cui; Xinsheng Gu; Jingshu Chen; Ying Xie; Sui Ke; Jing Wu; Andrei Golovko; Benjamin Morpurgo; Chunhong Yan; Timothy D. Phillips; Wen Xie; Jianyuan Luo; Zhijun Zhou; Yanan Tian. Pregnane X receptor regulates the AhR/Cyp1A1 pathway and protects liver cells from benzo-[α]-pyrene-induced DNA damage. Toxicology Letters 2017, 275, 67 -76.
AMA StyleHongmei Cui, Xinsheng Gu, Jingshu Chen, Ying Xie, Sui Ke, Jing Wu, Andrei Golovko, Benjamin Morpurgo, Chunhong Yan, Timothy D. Phillips, Wen Xie, Jianyuan Luo, Zhijun Zhou, Yanan Tian. Pregnane X receptor regulates the AhR/Cyp1A1 pathway and protects liver cells from benzo-[α]-pyrene-induced DNA damage. Toxicology Letters. 2017; 275 ():67-76.
Chicago/Turabian StyleHongmei Cui; Xinsheng Gu; Jingshu Chen; Ying Xie; Sui Ke; Jing Wu; Andrei Golovko; Benjamin Morpurgo; Chunhong Yan; Timothy D. Phillips; Wen Xie; Jianyuan Luo; Zhijun Zhou; Yanan Tian. 2017. "Pregnane X receptor regulates the AhR/Cyp1A1 pathway and protects liver cells from benzo-[α]-pyrene-induced DNA damage." Toxicology Letters 275, no. : 67-76.
// Liuqin He 1, 2, * , Huan Li 3, * , Niu Huang 3 , Xihong Zhou 1 , Junquan Tian 1, 2 , Tiejun Li 1, 4 , Jing Wu 3 , Yanan Tian 5 , Yulong Yin 1, 4 , Kang Yao 1, 4 1 Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences; Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture; Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production; Changsha, Hunan, 410125, China 2 University of Chinese Academy of Sciences, Beijing, 10008, China 3 College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China 4 Hunan Co-Innovation Center of Animal Production Safety, Changsha, Hunan, 410128, China 5 Department of Veterinary Physiology and Pharmacology, MS 4466, Texas A&M University, College Station, TX 77843, USA * These authors have contributed equally to this work Correspondence to: Yulong Yin, email: [email protected] Kang Yao, email: [email protected] Yanan Tian, email: [email protected] Keywords: AKG, pregnane X receptor, NF-κB, CYP450, intestinal inflammation Received: January 28, 2017 Accepted: March 17, 2017 Published: April 06, 2017 ABSTRACT Alpha-ketoglutarate (AKG) is a critical nutritional factor in the maintenance of intestinal homeostasis. However, the relative mechanism of AKG has not been well understood. It was recently shown that the interaction between nuclear factor kappa B (NF-κB)-mediated inflammatory pathway and pregnane X receptor (PXR)-regulated detoxification pathway is a check and balance mechanism for keeping the homeostatic state of the intestine, preventing the onset of intestinal inflammation which may lead to cancer. In the current study we used lipopolysaccharide (LPS)-challenged piglet and intestinal porcine epithelial cells-J2 models to investigate the effects of dietary AKG supplementation on the intestinal immune system and PXR regulated target expression. We found that LPS induced significant activation of the NF-κB-mediated inflammatory pathway with concomitant impairment of intestinal nutrient absorption. AKG administration increased intracellular AKG and its metabolite concentrations and enhanced the mRNA expression of alpha-ketoglutarate dehydrogenase in vivo and in vitro . Thus dietary AKG supplementation reversed the adverse effects induced by LPS. We also found a strong inhibitory effects on the NF-κB-mediated inflammatory pathway, especially, in the AKG-treated intestinal tissues, LPS-induced NF-κB phosphorylation was inhibited and TNF-α was suppressed. Interestingly, AKG has potent effects in regulating the PXR and its downstream targets such as CYP3As and CYP2Bs in vivo and in vitro , although AKG is not a known PXR ligand. One potential mechanism for the up-regulation of the PXR pathway is through the down-regulation of NF-κB pathway which in turn de-represses the PXR-regulated target expression. Taken together, our results suggest that AKG improves intestinal immune system through modulating the interaction between PXR and NF-κB. Our findings have important implications for the prevention and treatment of intestinal inflammatory diseases in neonates. Liuqin He1,2,*, Huan Li3,*, Niu Huang3, Xihong Zhou1, Junquan Tian1,2, Tiejun Li1,4, Jing Wu3, Yanan Tian5, Yulong Yin1,4, Kang Yao1,4 1Key Laboratory of Agro-ecological Processes in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences; Scientific Observing and Experimental Station of Animal Nutrition and Feed Science in South-Central, Ministry of Agriculture; Hunan Provincial Engineering Research Center for Healthy Livestock and Poultry Production; Changsha, Hunan, 410125, China 2University of Chinese Academy of Sciences, Beijing, 10008, China 3College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan, 410128, China 4Hunan Co-Innovation Center of Animal Production Safety, Changsha, Hunan, 410128, China 5Department of Veterinary Physiology and Pharmacology, MS 4466, Texas A&M University, College Station, TX 77843, USA *These authors have contributed equally to this work Correspondence to: Yulong Yin, email: [email protected] Kang Yao, email: [email protected] Yanan Tian, email: [email protected] Keywords: AKG, pregnane X receptor, NF-κB, CYP450, intestinal inflammation Received: January 28, 2017 Accepted: March 17, 2017 Published: April 06, 2017 ABSTRACT Alpha-ketoglutarate (AKG) is a critical nutritional factor in the maintenance of intestinal homeostasis. However, the relative mechanism of AKG has not been well understood. It was recently shown that the interaction between nuclear factor kappa B (NF-κB)-mediated inflammatory pathway and pregnane X receptor (PXR)-regulated detoxification pathway is a check and balance mechanism for keeping the homeostatic state of the intestine, preventing the onset of intestinal inflammation which may lead to cancer. In the current study we used lipopolysaccharide (LPS)-challenged piglet and intestinal porcine epithelial cells-J2 models to investigate the effects of dietary AKG supplementation on the intestinal immune system and PXR regulated target expression. We found that LPS induced significant activation of the NF-κB-mediated inflammatory pathway with concomitant impairment of intestinal nutrient absorption. AKG administration increased intracellular AKG and its metabolite concentrations and enhanced the mRNA expression of alpha-ketoglutarate dehydrogenase in vivo and in vitro. Thus dietary AKG supplementation reversed the adverse effects induced by LPS. We also found a strong inhibitory effects on the NF-κB-mediated inflammatory pathway, especially, in the AKG-treated intestinal tissues, LPS-induced NF-κB phosphorylation was inhibited and TNF-α was suppressed. Interestingly, AKG has potent...
Liuqin He; Huan Li; Niu Huang; Xihong Zhou; Junquan Tian; Tiejun Li; Jing Wu; Yanan Tian; Yulong Yin; Kang Yao. Alpha-ketoglutarate suppresses the NF-κB-mediated inflammatory pathway and enhances the PXR-regulated detoxification pathway. Oncotarget 2017, 8, 102974 -102988.
AMA StyleLiuqin He, Huan Li, Niu Huang, Xihong Zhou, Junquan Tian, Tiejun Li, Jing Wu, Yanan Tian, Yulong Yin, Kang Yao. Alpha-ketoglutarate suppresses the NF-κB-mediated inflammatory pathway and enhances the PXR-regulated detoxification pathway. Oncotarget. 2017; 8 (61):102974-102988.
Chicago/Turabian StyleLiuqin He; Huan Li; Niu Huang; Xihong Zhou; Junquan Tian; Tiejun Li; Jing Wu; Yanan Tian; Yulong Yin; Kang Yao. 2017. "Alpha-ketoglutarate suppresses the NF-κB-mediated inflammatory pathway and enhances the PXR-regulated detoxification pathway." Oncotarget 8, no. 61: 102974-102988.
T-2 toxin is a secondary metabolite produced by Fusarium genus and is a common contaminant in food and feedstuffs of cereal origin. In porcine granulosa cells(GC), T-2 toxin has been shown to inhibit the steroidogenesis; however, the mechanism has not been well understood. Gonadotropin-stimulated steroidogenesis is regulated by the cAMP-PKA pathway. In this study, we investigated potential mechanisms for T-2 toxin-induced reproductive toxicity focusing on the critical steps of the cAMP-PKA pathway affected by T-2 toxin. We first analyzed the effects of T-2 toxin on progesterone and estrogen production in rat granulosa cells. For this purpose the granulosa cells were cultured for 48 h in 10% fetal bovine serum-containing medium followed by 24h in serum-free medium containing FSH (10 ng/ml) and androstenedione (3 ng/ml), both are required for normal steroidogenesis. Treatment of these cells with T-2 toxin dose-dependently inhibited the growth of cells and the steroid hormone production. Cellular cyclic AMP levels were dose-dependently inhibited by T-2 toxin (0, 1, 10 and 100 nM, 24 h). Furthermore, we found that although the induction of progesterone by 8-Br-cAMP (a FSH mimetic) and 22R-HC (substrate for progesterone) could both be inhibited by T-2 toxin treatment, the T-2-imposed inhibitory effects could be reversed by increasing doses of 22R-HC, while increasing 8-Br-cAMP had no effects, suggesting that T2 toxin targeted at distinct mechanisms. cAMP-stimulated steroidogenic acute regulatory protein (StAR) is a rate limiting protein in progesterone synthesis. Exposure to T2 toxin caused significant suppression of StAR expression as determined by Western blotting and semi-quantitative RT-PCR suggesting StAR is a sensitive target for T-2 toxin. Taken together, our results strongly suggest that T2 toxin inhibits steroidogenesis by suppressing cAMP-PKA pathway and StAR is a target for T-2-toxin. The antisteroidogenesis effects were observable at low T-2 dose (1 ng/ml) suggesting T-2 toxin has an endocrine disruptive effect.
Jing Wu; Di Tu; Li-Yun Yuan; Jin-E Yi; Yanan Tian. T-2 toxin regulates steroid hormone secretion of rat ovarian granulosa cells through cAMP-PKA pathway. Toxicology Letters 2015, 232, 573 -579.
AMA StyleJing Wu, Di Tu, Li-Yun Yuan, Jin-E Yi, Yanan Tian. T-2 toxin regulates steroid hormone secretion of rat ovarian granulosa cells through cAMP-PKA pathway. Toxicology Letters. 2015; 232 (3):573-579.
Chicago/Turabian StyleJing Wu; Di Tu; Li-Yun Yuan; Jin-E Yi; Yanan Tian. 2015. "T-2 toxin regulates steroid hormone secretion of rat ovarian granulosa cells through cAMP-PKA pathway." Toxicology Letters 232, no. 3: 573-579.
The pregnane X receptor (PXR, NR1I2) is a ligand‐activated nuclear receptor which plays an essential role in organism's metabolic detoxification system by sensing the presence of xenobiotics and triggering detoxification responses. In addition to its role in xenobiotic metabolism, PXR has pleiotropic functions in regulating immune/inflammatory responses, cell proliferation, bile acid/cholesterol metabolism, glucose and lipid metabolism, steroid/endocrine homeostasis and bone metabolism. Recent research suggests that the PXR is required for maintaining healthy commensalism between microbiota and gut. Interestingly, the metabolites such as indole derivatives from commensal microbes serve as the ligands for the PXR in intestinal epithelium forming an intricate mutualistic interaction between host and microbiota. PXR‐regulated gene responses are controlled at epigenetic level by chromatin modifications, DNA methylation and noncoding RNA. Developmental alterations of the epigenome by exposure to the xenobiotics or diseases may produce persistent changes in PXR‐regulated physiological responses. These new areas of research promise to vastly increase our understanding of PXR‐regulated responses. In this review we highlight recent results on the epigenetic mechanisms for the PXR‐regulated gene expression and discuss the physiological significance of these findings. J. Cell. Physiol.
Xi Ma; Jingshu Chen; Yanan Tian. Pregnane X Receptor as the “Sensor and Effector” in Regulating Epigenome. Journal of Cellular Physiology 2014, 230, 752 -757.
AMA StyleXi Ma, Jingshu Chen, Yanan Tian. Pregnane X Receptor as the “Sensor and Effector” in Regulating Epigenome. Journal of Cellular Physiology. 2014; 230 (4):752-757.
Chicago/Turabian StyleXi Ma; Jingshu Chen; Yanan Tian. 2014. "Pregnane X Receptor as the “Sensor and Effector” in Regulating Epigenome." Journal of Cellular Physiology 230, no. 4: 752-757.
Pregnane X receptor (PXR, NR1I2) is a ligand-dependent nuclear receptor (NR) that functions as a xenobiotic sensor and effector in coordinately regulating expression of genes of the xenobiotic detoxification network. PXR exerts its transcriptional regulatory functions by dimerization with retinoic X receptor RXR, and PXR-RXR complex binds to specific DNA sequences for regulating gene expression. PXR functions are regulated at the epigenetic level by chromatin modifications, DNA methylation and noncoding RNA. Chromatin modifications are carried out, in part, through interaction with coregulator complexes, including steroid coactivators (SRCs), corepressors (NcoR/SMRT), hepatocyte nuclear factor 4 alpha, proliferator activated receptor γ coactivator 1 alpha and protein arginine methyltransferase 1. PXR can be modified by acetylation, phosphorylation and sumoylation, and the promoter of PXR can be methylated at the "CpG" island. These factors collectively determine the ways in which PXR activity can be regulated, thereby affecting the magnitude and duration of the PXR-regulated drug metabolic responses. Most studies of PXR focus on its role as a transcription factor, which is responsible for the generation of messenger RNA. Recent emerging evidence suggests that PXR regulates gene expression at both transcriptional and translational levels. This review highlights recent research on the epigenetic mechanisms that are found to be important for the gene-regulatory activity of PXR and discusses their implications in xenobiotic metabolism and adverse drug responses.
Yanan Tian. Epigenetic regulation of pregnane X receptor activity. Drug Metabolism Reviews 2013, 45, 166 -172.
AMA StyleYanan Tian. Epigenetic regulation of pregnane X receptor activity. Drug Metabolism Reviews. 2013; 45 (2):166-172.
Chicago/Turabian StyleYanan Tian. 2013. "Epigenetic regulation of pregnane X receptor activity." Drug Metabolism Reviews 45, no. 2: 166-172.
Pregnane X receptor (PXR) is a nuclear receptor that regulates the metabolism and disposition of various xenobiotics and endobioitics. We investigated a novel PXR function in regulating colon tumourigenesis in this study. Histochemistry, transfection, cell proliferation assay, anchorage-α-dependent assay, xenograft, immunohistochemistry, immunofluorescence flow cytometry. Using histochemistry analysis, we found that PXR expressions were lost or greatly diminished in many colon tumours. Ectopic expression of human PXR through stable transfection of PXR into colon cancer cell line HT29 significantly inhibited cell proliferation as determined by cell proliferation assay and anchorage-independent assay. Pregnane X receptor suppressed significantly HT29 xenograft tumour growth in nude mice compared with control (310±6.2 vs 120±6 mg, P<0.01). Immunohistochemistry and immunofluorescence analysis of Ki-67 on excised xenograft tumour tissues showed that PXR inhibited cancer cell proliferation. Furthermore, expressions of PXR and Ki-67 were mutually exclusive. The flow cytometry analysis indicated that PXR caused G0/G1 cell-cycle arrest. p21WAF1/CIP1 expression was markedly elevated whereas E2F1 expression was inhibited by PXR. PXR inhibits the proliferation and tumourigenicity of colon cancer cells by controlling cell cycle at G0/G1 cell phase by regulating p21WAF1/CIP1 and E2F/Rb pathways.
N Ouyang; S Ke; N Eagleton; Y Xie; G Chen; B Laffins; H Yao; B Zhou; Y Tian. Pregnane X receptor suppresses proliferation and tumourigenicity of colon cancer cells. British Journal of Cancer 2010, 102, 1753 -1761.
AMA StyleN Ouyang, S Ke, N Eagleton, Y Xie, G Chen, B Laffins, H Yao, B Zhou, Y Tian. Pregnane X receptor suppresses proliferation and tumourigenicity of colon cancer cells. British Journal of Cancer. 2010; 102 (12):1753-1761.
Chicago/Turabian StyleN Ouyang; S Ke; N Eagleton; Y Xie; G Chen; B Laffins; H Yao; B Zhou; Y Tian. 2010. "Pregnane X receptor suppresses proliferation and tumourigenicity of colon cancer cells." British Journal of Cancer 102, no. 12: 1753-1761.
Pregnane X receptor (PXR) is a ligand-dependent transcription factor, regulating gene expression of enzymes and transporters involved in xenobiotic/drug metabolism. Here, we report that protein arginine methyltransferase 1 (PRMT1) is required for the transcriptional activity of PXR. PRMT1 regulates expression of numerous genes, including nuclear receptor-regulated transcription, through methylating histone and non-histone proteins. Co-immunoprecipitation and histone methyltransferase assays revealed that PRMT1 is a major histone methyltransferase associated with PXR. The PXR ligand-binding domain is responsible for PXR-PRMT1 interaction as determined by mammalian two-hybrid and glutathione S-transferase (GST) pull-down assays. The chromatin immunoprecipitation (ChIP) assay showed that PRMT1 was recruited to the regulatory region of the PXR target gene cytochrome P450 3A4 (CYP3A4), with a concomitant methylation of arginine 3 of histone H4, in response to the PXR agonist rifampicin. In mammalian cells, small interfering RNA (siRNA) knockdown and gene deletion of PRMT1 greatly diminished the transcriptional activity of PXR, suggesting an indispensable role of PRMT1 in PXR-regulated gene expression. Interestingly, PXR appears to have a reciprocal effect on the PRMT1 functions by regulating its cellular compartmentalization as well as its substrate specificity. Taken together, these results demonstrated mutual interactions and functional interplays between PXR and PRMT1, and this interaction may be important for the epigenetics of PXR-regulated gene expression.
Ying Xie; Sui Ke; Nengtai Ouyang; Jinhan He; Wen Xie; Mark T. Bedford; Yanan Tian. Epigenetic Regulation of Transcriptional Activity of Pregnane X Receptor by Protein Arginine Methyltransferase 1. Journal of Biological Chemistry 2009, 284, 9199 -9205.
AMA StyleYing Xie, Sui Ke, Nengtai Ouyang, Jinhan He, Wen Xie, Mark T. Bedford, Yanan Tian. Epigenetic Regulation of Transcriptional Activity of Pregnane X Receptor by Protein Arginine Methyltransferase 1. Journal of Biological Chemistry. 2009; 284 (14):9199-9205.
Chicago/Turabian StyleYing Xie; Sui Ke; Nengtai Ouyang; Jinhan He; Wen Xie; Mark T. Bedford; Yanan Tian. 2009. "Epigenetic Regulation of Transcriptional Activity of Pregnane X Receptor by Protein Arginine Methyltransferase 1." Journal of Biological Chemistry 284, no. 14: 9199-9205.
The ChIP-chip technology has been used in a wide range of biomedical studies, such as identification of human transcription factor binding sites, investigation of DNA methylation, and investigation of histone modifications in animals and plants. Various methods have been proposed in the literature for analyzing the ChIP-chip data, such as the sliding window methods, the hidden Markov model-based methods, and Bayesian methods. Although, due to the integrated consideration of uncertainty of the models and model parameters, Bayesian methods can potentially work better than the other two classes of methods, the existing Bayesian methods do not perform satisfactorily. They usually require multiple replicates or some extra experimental information to parametrize the model, and long CPU time due to involving of MCMC simulations.
Mingqi Wu; Faming Liang; Yanan Tian. Bayesian modeling of ChIP-chip data using latent variables. BMC Bioinformatics 2009, 10, 352 -352.
AMA StyleMingqi Wu, Faming Liang, Yanan Tian. Bayesian modeling of ChIP-chip data using latent variables. BMC Bioinformatics. 2009; 10 (1):352-352.
Chicago/Turabian StyleMingqi Wu; Faming Liang; Yanan Tian. 2009. "Bayesian modeling of ChIP-chip data using latent variables." BMC Bioinformatics 10, no. 1: 352-352.
The aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor that belongs to the basic helix-loop-helix/Per-ARNT-Sim (bHLH-PAS) family. Its ligands include many natural and synthetic compounds, some of which, such as polyhalogenated aromatic hydrocarbons and polycyclic aromatic hydrocarbons, are important environmental contaminants. NF-κB is a pleiotropic factor that regulates many physiological and pathophysiological processes including the immune and inflammatory responses. In the past decade, accumulating evidence suggests close interactions between AhR and NF-κB pathways, and these interactions are potentially important mechanisms for many pathological processes such as the chemical-induced immune dysfunctions, carcinogenesis and alteration of xenobiotic metabolism and disposition. AhR–NF-κB interaction has become a mechanistic linchpin linking certain pathological responses induced by environmental insults. Furthermore, the AhR–NF-κB interaction provides basis for therapeutic applications of certain AhR ligands to treat human diseases. The effects of AhR–NF-κB on the epigenome are an important area that is not well understood. In this review, I highlight current research regarding the AhR–NF-κB(RelA) interactions with emphasis on the epigenetic impacts of these interactions on chromatin modifications and transcription elongation control.
Yanan Tian. Ah receptor and NF-κB interplay on the stage of epigenome. Biochemical Pharmacology 2008, 77, 670 -680.
AMA StyleYanan Tian. Ah receptor and NF-κB interplay on the stage of epigenome. Biochemical Pharmacology. 2008; 77 (4):670-680.
Chicago/Turabian StyleYanan Tian. 2008. "Ah receptor and NF-κB interplay on the stage of epigenome." Biochemical Pharmacology 77, no. 4: 670-680.
Pregnane X receptor (PXR) is a nuclear receptor that coordinately regulates transcriptional expression of both phase I and phase II metabolizing enzymes. PXR plays an important role in the pharmacokinetics of a broad spectrum of endogenous and xenobiotic compounds and appears to have evolved in part to protect organisms from toxic xenobiotics. Metabolism of benzo[a]pyrene (BaP), a well-established carcinogen and ubiquitous environmental contaminant, can result in either detoxification or bioactivation to its genotoxic forms. Therefore, PXR could modulate the genotoxicity of BaP by changing the balance of the metabolic pathways in favor of BaP detoxification. To examine the role of PXR in BaP genotoxicity, BaP–DNA adduct formation was measured by 32P-postlabeling in BaP-treated parental HepG2 cells and human PXR-transfected HepG2 cells. The presence of transfected PXR significantly reduced the level of adducts relative to parental cells by 50–65% (p < 0.001), demonstrating that PXR protects liver cells from genotoxicity induced by exposure to BaP. To analyze potential PXR-regulated detoxification pathways in liver cells, a panel of genes involved in phase I and phase II metabolism and excretion was surveyed with real-time quantitative reverse transcription PCR. The messenger RNA levels of CYP1A2, GSTA1, GSTA2, GSTM1, UGT1A6, and BCRP (ABCG2) were significantly higher in cells overexpressing PXR, independent of exposure to BaP. In addition, the total GST enzymatic activity, which favors the metabolic detoxification of BaP, was significantly increased by the presence of PXR (p < 0.001), independent of BaP exposure. Taken together, these results suggest that PXR plays an important role in protection against DNA damage by polycyclic aromatic hydrocarbons (PAHs) such as BaP, and that these protective effects may be through a coordinated regulation of genes involved in xenobiotic metabolism.
Christine Naspinski; Xinsheng Gu; Guo-Dong Zhou; Susanne U. Mertens-Talcott; Kirby C. Donnelly; Yanan Tian. Pregnane X Receptor Protects HepG2 Cells from BaP-Induced DNA Damage. Toxicological Sciences 2008, 104, 67 -73.
AMA StyleChristine Naspinski, Xinsheng Gu, Guo-Dong Zhou, Susanne U. Mertens-Talcott, Kirby C. Donnelly, Yanan Tian. Pregnane X Receptor Protects HepG2 Cells from BaP-Induced DNA Damage. Toxicological Sciences. 2008; 104 (1):67-73.
Chicago/Turabian StyleChristine Naspinski; Xinsheng Gu; Guo-Dong Zhou; Susanne U. Mertens-Talcott; Kirby C. Donnelly; Yanan Tian. 2008. "Pregnane X Receptor Protects HepG2 Cells from BaP-Induced DNA Damage." Toxicological Sciences 104, no. 1: 67-73.
It is a long-standing observation that inflammatory responses and infections decrease drug metabolism capacity in human and experimental animals. Cytochrome P-450 3A4 cyp304 is responsible for the metabolism of over 50% of current prescription drugs, and cyp3a4 expression is transcriptionally regulated by pregnane X receptor (PXR), which is a ligand-dependent transcription factor. In this study, we report that NF-κB activation by lipopolysaccharide and tumor necrosis factor-α plays a pivotal role in the suppression of cyp3a4 through interactions of NF-κB with the PXR·retinoid X receptor (RXR) complex. Inhibition of NF-κB by NF-κB-specific suppressor SRIκBα reversed the suppressive effects of lipopolysaccharide and tumor necrosis factor-α. Furthermore, we showed that NF-κB p65 disrupted the association of the PXR·RXRα complex with DNA sequences as determined by electrophoretic mobility shift assay and chromatin immunoprecipitation assays. NF-κB p65 directly interacted with the DNA-binding domain of RXRα and may prevent its binding to the consensus DNA sequences, thus inhibiting the transactivation by the PXR·RXRα complex. This mechanism of suppression by NF-κB activation may be extended to other nuclear receptor-regulated systems where RXRα is a dimerization partner.
Xinsheng Gu; Sui Ke; Duan Liu; Tao Sheng; Paul E. Thomas; Arnold B. Rabson; Michael A. Gallo; Wen Xie; Yanan Tian. Role of NF-κB in Regulation of PXR-mediated Gene Expression. Journal of Biological Chemistry 2006, 281, 17882 -17889.
AMA StyleXinsheng Gu, Sui Ke, Duan Liu, Tao Sheng, Paul E. Thomas, Arnold B. Rabson, Michael A. Gallo, Wen Xie, Yanan Tian. Role of NF-κB in Regulation of PXR-mediated Gene Expression. Journal of Biological Chemistry. 2006; 281 (26):17882-17889.
Chicago/Turabian StyleXinsheng Gu; Sui Ke; Duan Liu; Tao Sheng; Paul E. Thomas; Arnold B. Rabson; Michael A. Gallo; Wen Xie; Yanan Tian. 2006. "Role of NF-κB in Regulation of PXR-mediated Gene Expression." Journal of Biological Chemistry 281, no. 26: 17882-17889.
The expression of the cytochrome P450 1A1 gene (cyp1a1) is regulated by the aryl hydrocarbon receptor (AhR), which is a ligand-activated transcription factor that mediates most toxic responses induced by 2,3,7,8tetrachlorodibenzo-p-dioxin (TCDD). In the nucleus, ligand-activated AhR binds to the xenobiotic response elements, initiating chromatin remodeling and recruitment of coregulators, leading to the formation of preinitiation complex followed by elongation. Here, we report that ligand-activated AhR recruits the positive transcription elongation factor (P-TEFb) and RNA polymerase II (RNA PII) to the cyp1a1 promoter with concomitant phosphorylation of the RNA PII carboxyl domain (CTD). Interestingly, the serine 2 and serine 5 of the heptapeptide repeats (YSPTSPS) were sequentially phosphorylated upon TCDD treatment. Inhibition of P-TEFb kinase activity by 5,6-dichloro-1-β-d-ribofuranosyl-benzimidazole (DRB) suppressed CTD phosphorylation (especially serine 2 phosphorylation) and abolished processive elongation without disrupting the assembly of the preinitiation complex at the cyp1a1 promoter. Remarkably, we found that activation of NF-κB by TNF-α selectively inhibited TCDD-induced serine 2 phosphorylation in mouse liver cells, suggesting that residue-specific phosphorylation of RNA PII CTD at the cyp1a1 promoter is an important regulatory point upon which signal “cross-talk” converges. Finally, we show that ligand-activated AhR associated with P-TEFb through the C terminus of cyclin T1, suggesting that AhR recruit the P-TEFb to the cyp1a1 promoter whereupon its kinase subunit phosphorylates the RNA PII CTD.
Yanan Tian; Sui Ke; Min Chen; Tao Sheng. Interactions between the Aryl Hydrocarbon Receptor and P-TEFb. Journal of Biological Chemistry 2003, 278, 44041 -44048.
AMA StyleYanan Tian, Sui Ke, Min Chen, Tao Sheng. Interactions between the Aryl Hydrocarbon Receptor and P-TEFb. Journal of Biological Chemistry. 2003; 278 (45):44041-44048.
Chicago/Turabian StyleYanan Tian; Sui Ke; Min Chen; Tao Sheng. 2003. "Interactions between the Aryl Hydrocarbon Receptor and P-TEFb." Journal of Biological Chemistry 278, no. 45: 44041-44048.