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T-2 toxin, which is mainly produced by specific strains of Fusarium in nature, can induce immunotoxicity and oxidative stress, resulting in immune organ dysfunction and apoptosis. Betulinic acid (BA), a pentacyclic triterpenoids from nature plants, has been demonstrated to possess immunomodulating and antioxidative bioactivities. The purpose of the study was to explore the effect of BA on T-2 toxin-challenged spleen oxidative damage and further elucidate the underlying mechanism. We found that BA not only ameliorated the contents of serum total cholesterol (TC) and triglyceride (TG) but also restored the number of lymphocytes in T-2 toxin-induced mice. BA dose-dependently reduced the accumulation of reactive oxygen species (ROS), enhanced superoxide dismutase (SOD) activity, and decreased malondialdehyde (MDA) content, as well as increased the total antioxidant capacity (T-AOC) in the spleen of T-2-toxin-exposed mice. Moreover, BA reduced inflammatory cell infiltration in the spleen, improved the morphology of mitochondria and enriched the number of organelles in splenocytes, and dramatically attenuated T-2 toxin-triggered splenocyte apoptosis. Furthermore, administration of BA alleviated the protein phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinases (ERK); decreased the protein expression of kelch-like erythroid cell-derived protein with CNC homology [ECH]-associated protein1 (Keap1); and increased the protein expression of nuclear factor erythroid 2 [NF-E2]-related factor (Nrf2) and heme oxygenase-1 (HO-1) in the spleen. These findings demonstrate that BA defends against spleen oxidative damage associated with T-2 toxin injection by decreasing ROS accumulation and activating the Nrf2 signaling pathway, as well as inhibiting the mitogen-activated protein kinase (MAPK) signaling pathway.
Li Kong; Lijuan Zhu; Xianglian Yi; You Huang; Haoqiang Zhao; Yazhi Chen; Zhihang Yuan; Lixin Wen; Jing Wu; Jine Yi. Betulinic Acid Alleviates Spleen Oxidative Damage Induced by Acute Intraperitoneal Exposure to T-2 Toxin by Activating Nrf2 and Inhibiting MAPK Signaling Pathways. Antioxidants 2021, 10, 158 .
AMA StyleLi Kong, Lijuan Zhu, Xianglian Yi, You Huang, Haoqiang Zhao, Yazhi Chen, Zhihang Yuan, Lixin Wen, Jing Wu, Jine Yi. Betulinic Acid Alleviates Spleen Oxidative Damage Induced by Acute Intraperitoneal Exposure to T-2 Toxin by Activating Nrf2 and Inhibiting MAPK Signaling Pathways. Antioxidants. 2021; 10 (2):158.
Chicago/Turabian StyleLi Kong; Lijuan Zhu; Xianglian Yi; You Huang; Haoqiang Zhao; Yazhi Chen; Zhihang Yuan; Lixin Wen; Jing Wu; Jine Yi. 2021. "Betulinic Acid Alleviates Spleen Oxidative Damage Induced by Acute Intraperitoneal Exposure to T-2 Toxin by Activating Nrf2 and Inhibiting MAPK Signaling Pathways." Antioxidants 10, no. 2: 158.
T-2 toxin, a trichothecene mycotoxin produced by Fusarium, is widely distributed in crops and animal feed and frequently induces intestinal damage. Betulinic acid (BA), a plant-derived pentacyclic lupane-type triterpene, possesses potential immunomodulatory, antioxidant and anti-inflammatory biological properties. The current study aimed to explore the protective effect and molecular mechanisms of BA on intestinal mucosal impairment provoked by acute exposure to T-2 toxin. Mice were intragastrically administered BA (0.25, 0.5, or 1 mg/kg) daily for 2 weeks and then injected intraperitoneally with T-2 toxin (4 mg/kg) once to induce an intestinal impairment. BA pretreatment inhibited the loss of antioxidant capacity in the intestine of T-2 toxin-treated mice by elevating the levels of CAT, GSH-PX and GSH and reducing the accumulation of MDA. In addition, BA pretreatment alleviated the T-2 toxin-triggered intestinal immune barrier dysregulation by increasing the SIgA level in the intestine at dosages of 0.5 and 1 mg/kg, increasing IgG and IgM levels in serum at dosages of 0.5 and 1 mg/kg and restoring the intestinal C3 and C4 levels at a dosage of 1 mg/kg. BA administration at a dosage of 1 mg/kg also improved the intestinal chemical barrier by decreasing the serum level of DAO. Moreover, BA pretreatment improved the intestinal physical barrier via boosting the expression of ZO-1 and Occludin mRNAs and restoring the morphology of intestinal villi that was altered by T-2 toxin. Furthermore, treatment with 1 mg/kg BA downregulated the expression of p-NF-κB and p-IκB-α proteins in the intestine, while all doses of BA suppressed the pro-inflammatory cytokines expression of IL-1β, IL-6 and TNF-α mRNAs and increased the anti-inflammatory cytokine expression of IL-10 mRNA in the intestine of T-2 toxin-exposed mice. BA was proposed to exert a protective effect on intestinal mucosal disruption in T-2 toxin-stimulated mice by enhancing the intestinal antioxidant capacity, inhibiting the secretion of inflammatory cytokines and repairing intestinal mucosal barrier functions, which may be associated with BA-mediated inhibition of the NF-κB signaling pathway activation.
Chenxi Luo; Chenglong Huang; Lijuan Zhu; Li Kong; Zhihang Yuan; Lixin Wen; Rongfang Li; Jing Wu; Jine Yi. Betulinic Acid Ameliorates the T-2 Toxin-Triggered Intestinal Impairment in Mice by Inhibiting Inflammation and Mucosal Barrier Dysfunction through the NF-κB Signaling Pathway. Toxins 2020, 12, 794 .
AMA StyleChenxi Luo, Chenglong Huang, Lijuan Zhu, Li Kong, Zhihang Yuan, Lixin Wen, Rongfang Li, Jing Wu, Jine Yi. Betulinic Acid Ameliorates the T-2 Toxin-Triggered Intestinal Impairment in Mice by Inhibiting Inflammation and Mucosal Barrier Dysfunction through the NF-κB Signaling Pathway. Toxins. 2020; 12 (12):794.
Chicago/Turabian StyleChenxi Luo; Chenglong Huang; Lijuan Zhu; Li Kong; Zhihang Yuan; Lixin Wen; Rongfang Li; Jing Wu; Jine Yi. 2020. "Betulinic Acid Ameliorates the T-2 Toxin-Triggered Intestinal Impairment in Mice by Inhibiting Inflammation and Mucosal Barrier Dysfunction through the NF-κB Signaling Pathway." Toxins 12, no. 12: 794.
T-2 toxin, the most toxic of the trichothecenes, is widely found in grains and feeds, and its intake poses serious risks to the health of humans and animals. An important cytotoxicity mechanism of T-2 toxin is the production of excess free radicals, which in turn leads to oxidative stress. Betulinic acid (BA) has many biological activities, including antioxidant activity, which is a plant-derived pentacyclic triterpenoid. The protective effects and mechanisms of BA in blocking oxidative stress caused by acute exposure to T-2 toxin in the thymus of mice was studied. BA pretreatment reduced ROS production, decreased the MDA content, and increased the content of IgG in serum and the levels of SOD and GSH in the thymus. BA pretreatment also reduced the degree of congestion observed in histopathological tissue sections of the thymus induced by T-2 toxin. Besides, BA downregulated the phosphorylation of the p38, JNK, and ERK proteins, while it upregulated the expression of the Nrf2 and HO-1 proteins in thymus tissues. The results indicated that BA could protect the thymus against the oxidative damage challenged by T-2 toxin by activating Nrf2 and suppressing the MAPK signaling pathway.
Lijuan Zhu; Xianglian Yi; Chaoyang Ma; Chenxi Luo; Li Kong; Xing Lin; Xinyu Gao; Zhihang Yuan; Lixin Wen; Rongfang Li; Jing Wu; Jine Yi. Betulinic Acid Attenuates Oxidative Stress in the Thymus Induced by Acute Exposure to T-2 Toxin via Regulation of the MAPK/Nrf2 Signaling Pathway. Toxins 2020, 12, 540 .
AMA StyleLijuan Zhu, Xianglian Yi, Chaoyang Ma, Chenxi Luo, Li Kong, Xing Lin, Xinyu Gao, Zhihang Yuan, Lixin Wen, Rongfang Li, Jing Wu, Jine Yi. Betulinic Acid Attenuates Oxidative Stress in the Thymus Induced by Acute Exposure to T-2 Toxin via Regulation of the MAPK/Nrf2 Signaling Pathway. Toxins. 2020; 12 (9):540.
Chicago/Turabian StyleLijuan Zhu; Xianglian Yi; Chaoyang Ma; Chenxi Luo; Li Kong; Xing Lin; Xinyu Gao; Zhihang Yuan; Lixin Wen; Rongfang Li; Jing Wu; Jine Yi. 2020. "Betulinic Acid Attenuates Oxidative Stress in the Thymus Induced by Acute Exposure to T-2 Toxin via Regulation of the MAPK/Nrf2 Signaling Pathway." Toxins 12, no. 9: 540.
This study was conducted to assess the growth performance and immunological effects of vaccination-induced stress on broilers. The chickens were administered 0, 2, 4, 8, and 16 doses of live LaSota Newcastle disease (ND) vaccine and slaughtered on the 1st, 7th, 14th, and 21st day post vaccination. The results showed that the serum antibody titers after Newcastle disease virus (NDV) vaccination were elevated at day 7 post vaccination, peaked at day 14, then declined by day 21. Interestingly, the antibody titers peaked at 2 doses, and no further dose-dependent titer increases were observed. This study demonstrated that vaccination-induced stress increased serum adrenocorticotropic hormone and cortisol, affected growth performance (average daily gain, average daily feed intake, and feed conversion ratio), and triggered apoptosis in spleen lymphocytes by downregulating the ratio of Bcl-2 to BAX and upregulating the gene expressions of caspase-3 and -9, which was concordant with the activation of the enzymatic activities of caspase-3 and -9. This study suggests that NDV vaccine doses in broilers must be controlled judiciously because increasing the number of doses resulted in increased lymphocyte apoptosis while the peak of the antibody titer and optimal growth performance were achieved at a low number of doses (2 doses).
R.F. Li; S.P. Liu; Z.H. Yuan; J.E. Yi; Y.N. Tian; J. Wu; L.X. Wen. Effects of induced stress from the live LaSota Newcastle disease vaccination on the growth performance and immune function in broiler chickens. Poultry Science 2020, 99, 1896 -1905.
AMA StyleR.F. Li, S.P. Liu, Z.H. Yuan, J.E. Yi, Y.N. Tian, J. Wu, L.X. Wen. Effects of induced stress from the live LaSota Newcastle disease vaccination on the growth performance and immune function in broiler chickens. Poultry Science. 2020; 99 (4):1896-1905.
Chicago/Turabian StyleR.F. Li; S.P. Liu; Z.H. Yuan; J.E. Yi; Y.N. Tian; J. Wu; L.X. Wen. 2020. "Effects of induced stress from the live LaSota Newcastle disease vaccination on the growth performance and immune function in broiler chickens." Poultry Science 99, no. 4: 1896-1905.
The aim of this study is to confirm the toxic effect of phenylethyl isothiocyanate (PEITC) on porcine kidney cells (PK-15) and explore the effect of oxidative damage mediated by reactive oxygen species (ROS) induced by PEITC in PK-15 cells. Porcine kidney cell line (PK-15) was treated with PEITC (2, 5, and 10 µM) for 24 hours, and the oxidative damage mediated by PEITC through ROS was investigated. The survival rate of PK-15 cells decreased in a dose-dependent manner after the treatment of PEITC in a dose-dependent manner. A high concentration of PEITC (10 µM) can change cell morphology, increase the content of malondialdehyde, ROS, and lactate dehydrogenase, and decrease the activity of SOD, CAT, GSH-PX, and GSH. PEITC has a toxic effect on PK-15 cells by inducing oxidative stress in PK-15 cells through the generation of ROS.
Yuanyuan Zhu; Shuiping Liu; Sisi Yan; Ji Wang; Linyu Zhang; Xin Li; Lixin Wen; Jing Wu. Phenylethyl isothiocyanate induces oxidative damage of porcine kidney cells mediated by reactive oxygen species. Journal of Biochemical and Molecular Toxicology 2019, 34, e22428 .
AMA StyleYuanyuan Zhu, Shuiping Liu, Sisi Yan, Ji Wang, Linyu Zhang, Xin Li, Lixin Wen, Jing Wu. Phenylethyl isothiocyanate induces oxidative damage of porcine kidney cells mediated by reactive oxygen species. Journal of Biochemical and Molecular Toxicology. 2019; 34 (2):e22428.
Chicago/Turabian StyleYuanyuan Zhu; Shuiping Liu; Sisi Yan; Ji Wang; Linyu Zhang; Xin Li; Lixin Wen; Jing Wu. 2019. "Phenylethyl isothiocyanate induces oxidative damage of porcine kidney cells mediated by reactive oxygen species." Journal of Biochemical and Molecular Toxicology 34, no. 2: e22428.
T-2 toxin is one of the most toxic type A trichothecene mycotoxins in nature, and it exhibits reproductive toxicity. Betulinic acid (BA) is a natural pentacyclic triterpene compound found in species of Betula, and it has been reported to have antioxidant activity. The aim of the present study was to investigate the protective effect of BA on T-2-toxin-induced testicular injury in mice and explore its molecular mechanism. Sixty adult male mice were randomly divided into groups. The mice were pretreated orally with BA (0.25, 0.5, and 1.0 mg/kg) daily for 14 days, and the T-2 toxin (4 mg/kg body weight) was administered via intraperitoneal injection to induce oxidative stress after the last administration of BA. BA pretreatment significantly increased the secreted levels of testosterone and sperm motility. Moreover, BA pretreatment significantly increased the total antioxidant capacity (T-AOC), the activity of SOD and CAT, and the content of GSH, and it reduced the content of MDA. Furthermore, BA relieved testicular injury and reduced the number of apoptotic cells, and it significantly decreased the protein expression of Janus kinase 2 (JAK2), signal transducers and activators of transcription 3 (STAT3), caspsae-3, and Bcl-2-associated X protein (Bax). BA also increased the expression of B-cell lymphoma-2 (Bcl-2). We suggest that BA reduced the oxidative damage induced by T-2 toxin, and that these protective effects may be partially mediated by the JAK2/STAT3 signaling pathway.
Jing Wu; Chenglin Yang; Juan Liu; Jiaxin Chen; Chao Huang; Ji Wang; Zengenni Liang; Lixin Wen; Jin-E Yi; Zhihang Yuan. Betulinic Acid Attenuates T-2-Toxin-Induced Testis Oxidative Damage Through Regulation of the JAK2/STAT3 Signaling Pathway in Mice. Biomolecules 2019, 9, 787 .
AMA StyleJing Wu, Chenglin Yang, Juan Liu, Jiaxin Chen, Chao Huang, Ji Wang, Zengenni Liang, Lixin Wen, Jin-E Yi, Zhihang Yuan. Betulinic Acid Attenuates T-2-Toxin-Induced Testis Oxidative Damage Through Regulation of the JAK2/STAT3 Signaling Pathway in Mice. Biomolecules. 2019; 9 (12):787.
Chicago/Turabian StyleJing Wu; Chenglin Yang; Juan Liu; Jiaxin Chen; Chao Huang; Ji Wang; Zengenni Liang; Lixin Wen; Jin-E Yi; Zhihang Yuan. 2019. "Betulinic Acid Attenuates T-2-Toxin-Induced Testis Oxidative Damage Through Regulation of the JAK2/STAT3 Signaling Pathway in Mice." Biomolecules 9, no. 12: 787.
In the past decades, hepatocellular carcinoma (HCC) has been receiving increased attention due to rising morbidity and mortality in both developing and developed countries. Koumine, one of the significant alkaloidal constituents of Gelsemium elegans Benth., has been regarded as a promising anti-inflammation, anxiolytic, and analgesic agent, as well as an anti-tumor agent. In the present study, we attempted to provide a novel mechanism by which koumine suppresses HCC cell proliferation. We demonstrated that koumine might suppress the proliferation of HCC cells and promote apoptosis in HCC cells dose-dependently. Under koumine treatment, the mitochondria membrane potential was significantly decreased while reactive oxygen species (ROS) production was increased in HCC cells; in the meantime, the phosphorylation of ERK, p38, p65, and IκBα could all be inhibited by koumine treatment dose-dependently. More importantly, the effects of koumine upon mitochondria membrane potential, ROS production, and the phosphorylation of ERK, p38, p65, and IκBα could be significantly reversed by ROS inhibitor, indicating that koumine affects HCC cell fate and ERK/p38 MAPK and NF-κB signaling activity through producing excess ROS. In conclusion, koumine could inhibit the proliferation of HCC cells and promote apoptosis in HCC cells; NF-κB and ERK/p38 MAPK pathways could contribute to koumine functions in a ROS-dependent manner.
Zhihang Yuan; Zengenni Liang; Jine Yi; Xiaojun Chen; Rongfang Li; Jing Wu; Zhiliang Sun. Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling. Biomolecules 2019, 9, 559 .
AMA StyleZhihang Yuan, Zengenni Liang, Jine Yi, Xiaojun Chen, Rongfang Li, Jing Wu, Zhiliang Sun. Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling. Biomolecules. 2019; 9 (10):559.
Chicago/Turabian StyleZhihang Yuan; Zengenni Liang; Jine Yi; Xiaojun Chen; Rongfang Li; Jing Wu; Zhiliang Sun. 2019. "Koumine Promotes ROS Production to Suppress Hepatocellular Carcinoma Cell Proliferation Via NF-κB and ERK/p38 MAPK Signaling." Biomolecules 9, no. 10: 559.
Phenethyl isothiocyanate (PEITC) is one of the glucosinolates (GLs) present in cruciferous vegetables. Although there are many reports of livestock and poultry poisoning caused by plants containing GLs, the actual dosage that causes poisoning and the characteristics of GLs and their metabolites are unclear. Herein, we investigated the inhibitory effects of PEITC on IPEC-J2 cells and examined the mechanisms of PEITC-induced apoptosis via the mitochondrial pathway. Cell viability was determined by the MTT assay, and the levels of reactive oxygen species, mitochondrial membrane potential (∆Ψ), intracellular Ca2+ concentration, and cell apoptosis were detected by flow cytometry. IPEC-J2 cells were collected to assess the activities of superoxide dismutase, catalase, and glutathione peroxidase, as well as the contents of glutathione, malondialdehyde, H2O2, ATP, and lactate dehydrogenase, using biochemical methods. The levels of cytochrome c, Bax, Bcl-2, caspase-3, caspase-9, poly (ADP-ribose) polymerase (PARP)-1, p53, CDC25C, and cyclin A2 were analyzed by western blotting. We found that PEITC effectively inhibited the growth of IPEC-J2 cells, causing apoptosis. PEITC suppressed the level of mitochondrial membrane potential; released cytochrome c from the mitochondria to the cytoplasm; reduced ATP levels; inhibited Bcl-2 expression; increased Bax expression; and activated caspase-9, caspase-3, and PARP-1, leading to apoptosis. PEITC also induced G2/M and S phase arrest by affecting cell cycle-associated proteins such as p53, CDC25C, and cyclin A2. We conclude that PEITC causes oxidative stress, cell cycle arrest, and apoptosis in IPEC-J2 cells via a mitochondrial-dependent Bax/Bcl-2 pathway.
Shuiping Liu; Yuanyuan Zhu; Sisi Yan; Haisi Xiao; Jine Yi; Rongfang Li; Jing Wu; Lixin Wen. Phenethyl isothiocyanate induces IPEC-J2 cells cytotoxicity and apoptosis via S-G2/M phase arrest and mitochondria-mediated Bax/Bcl-2 pathway. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 2019, 226, 108574 .
AMA StyleShuiping Liu, Yuanyuan Zhu, Sisi Yan, Haisi Xiao, Jine Yi, Rongfang Li, Jing Wu, Lixin Wen. Phenethyl isothiocyanate induces IPEC-J2 cells cytotoxicity and apoptosis via S-G2/M phase arrest and mitochondria-mediated Bax/Bcl-2 pathway. Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology. 2019; 226 ():108574.
Chicago/Turabian StyleShuiping Liu; Yuanyuan Zhu; Sisi Yan; Haisi Xiao; Jine Yi; Rongfang Li; Jing Wu; Lixin Wen. 2019. "Phenethyl isothiocyanate induces IPEC-J2 cells cytotoxicity and apoptosis via S-G2/M phase arrest and mitochondria-mediated Bax/Bcl-2 pathway." Comparative Biochemistry and Physiology Part C: Toxicology & Pharmacology 226, no. : 108574.
The presence of tannic acid (TA), which is widely distributed in plants, limits the utilization of non-grain feed. Illustrating the toxicity mechanism of TA in animals is important for preventing poisoning and for clinical development of TA. The aim of the present study was to evaluate the toxic effects and possible action mechanism of TA in porcine intestinal IPEC-J2 cells, as well as cell proliferation, apoptosis, and cell cycle. We investigated the toxic effects of TA in IPEC-J2 cells combining the analysis of TA-induced apoptotic responses and effect on the cell cycle. The results revealed that TA is highly toxic to IPEC-J2 cells. The stress-inducible factors reactive oxygen species, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine were increased in response to TA. Furthermore, TA suppressed mitochondrial membrane potential, reduced adenosine triphosphate production, and adversely affected B-cell lymphoma-2 (Bcl-2), Bcl-2-associated X protein, caspase-9, caspase-3, cytochrome c, cyclin A, cyclin-dependent kinases, ataxia-telangiectasia mutated, and P53 expression in a dose-dependent manner. We suggest that TA induces the mitochondrial pathway of apoptosis and S phase arrest in IPEC-J2 cells.
Ji Wang; Haisi Xiao; Yuanyuan Zhu; Shuiping Liu; Zhihang Yuan; Jing Wu; Lixin Wen. Tannic Acid Induces the Mitochondrial Pathway of Apoptosis and S Phase Arrest in Porcine Intestinal IPEC-J2 Cells. Toxins 2019, 11, 397 .
AMA StyleJi Wang, Haisi Xiao, Yuanyuan Zhu, Shuiping Liu, Zhihang Yuan, Jing Wu, Lixin Wen. Tannic Acid Induces the Mitochondrial Pathway of Apoptosis and S Phase Arrest in Porcine Intestinal IPEC-J2 Cells. Toxins. 2019; 11 (7):397.
Chicago/Turabian StyleJi Wang; Haisi Xiao; Yuanyuan Zhu; Shuiping Liu; Zhihang Yuan; Jing Wu; Lixin Wen. 2019. "Tannic Acid Induces the Mitochondrial Pathway of Apoptosis and S Phase Arrest in Porcine Intestinal IPEC-J2 Cells." Toxins 11, no. 7: 397.
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.
Although mTOR (the mammalian target of rapamycin) can regulate intracellular free Ca2+concentration in normal cultured podocytes, it remains elusive as to how mTORC2/AKT-mediated Ca2+participates in the process of T-2 toxin-induced apoptosis. The potential signaling responsible for intracellular Ca2+ concentration changes was investigated using immunoblot assays in an in vitro model of TM3 cell injury induced by T-2 toxin. Changes in Ca2+ were assessed using the Ca2+-sensitive fluorescent indictor dye Fura 2-AM. The cytotoxicity of TM3 cells was assessed with an MTT bioassay, and apoptosis was measured using Annexin V-FITC staining. Following T-2 toxin treatment, the growth of cells, phospho-mTORSer2481, phospho-mTORSer2448, and phospho-AktSer473 were significantly decreased in a time-dependent manner, whereas Ca2+ and apoptosis were increased. T-2 toxin-induced apoptosis was prevented by BAPTA-AM (a Ca2+chelator) and MHY1485 (an mTOR activator), and the application of mTOR activator MHY1485 also prevented the increase of intracellular free Ca2+concentration in TM3 cells. Our results strongly suggest that T-2 toxin exposure induces apoptosis in TM3 cells by inhibiting mTORC2/AKT to promote Ca2+ production.
Ji Wang; Chenglin Yang; Zhihang Yuan; Jine Yi; Jing Wu. T-2 Toxin Exposure Induces Apoptosis in TM3 Cells by Inhibiting Mammalian Target of Rapamycin/Serine/Threonine Protein Kinase(mTORC2/AKT) to Promote Ca2+Production. International Journal of Molecular Sciences 2018, 19, 3360 .
AMA StyleJi Wang, Chenglin Yang, Zhihang Yuan, Jine Yi, Jing Wu. T-2 Toxin Exposure Induces Apoptosis in TM3 Cells by Inhibiting Mammalian Target of Rapamycin/Serine/Threonine Protein Kinase(mTORC2/AKT) to Promote Ca2+Production. International Journal of Molecular Sciences. 2018; 19 (11):3360.
Chicago/Turabian StyleJi Wang; Chenglin Yang; Zhihang Yuan; Jine Yi; Jing Wu. 2018. "T-2 Toxin Exposure Induces Apoptosis in TM3 Cells by Inhibiting Mammalian Target of Rapamycin/Serine/Threonine Protein Kinase(mTORC2/AKT) to Promote Ca2+Production." International Journal of Molecular Sciences 19, no. 11: 3360.