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The movement disorder Parkinson’s disease (PD) is the second most frequently diagnosed neurodegenerative disease, and is associated with aging, the environment, and genetic factors. The intracellular aggregation of α-synuclein and the loss of dopaminergic neurons in the substantia nigra pars compacta are the pathological hallmark of PD. At present, there is no successful treatment for PD. Maackiain (MK) is a flavonoid extracted from dried roots of Sophora flavescens Aiton. MK has emerged as a novel agent for PD treatment that acts by inhibiting monoamine oxidase B. In this study, we assessed the neuroprotective potential of MK in Caenorhabditis elegans and investigated possible mechanism of this neuroprotection in the human SH-SY5Y cell line. We found that MK significantly reduced dopaminergic neuron damage in 6-hydroxydopamine (6-OHDA)-exposed worms of the BZ555 strain, with corresponding improvements in food-sensing behavior and life-span. In transgenic worms of strain NL5901 treated with 0.25 mM MK, the accumulation of α-synuclein was diminished by 27% (p < 0.01) compared with that in untreated worms. Moreover, in worms and the SH-SY5Y cell line, we confirmed that the mechanism of MK-mediated protection against PD pathology may include blocking apoptosis, enhancing the ubiquitin-proteasome system, and augmenting autophagy by increasing PINK1/parkin expression. The use of small interfering RNA to downregulate parkin expression in vivo and in vitro could reverse the benefits of MK in PD models. MK may have considerable therapeutic applications in PD.
Rong-Tzong Tsai; Chia-Wen Tsai; Shih-Ping Liu; Jia-Xin Gao; Yun-Hua Kuo; Pei-Min Chao; Huey-Shan Hung; Woei-Cherng Shyu; Shinn-Zong Lin; Ru-Huei Fu. Maackiain Ameliorates 6-Hydroxydopamine and SNCA Pathologies by Modulating the PINK1/Parkin Pathway in Models of Parkinson’s Disease in Caenorhabditis elegans and the SH-SY5Y Cell Line. International Journal of Molecular Sciences 2020, 21, 4455 .
AMA StyleRong-Tzong Tsai, Chia-Wen Tsai, Shih-Ping Liu, Jia-Xin Gao, Yun-Hua Kuo, Pei-Min Chao, Huey-Shan Hung, Woei-Cherng Shyu, Shinn-Zong Lin, Ru-Huei Fu. Maackiain Ameliorates 6-Hydroxydopamine and SNCA Pathologies by Modulating the PINK1/Parkin Pathway in Models of Parkinson’s Disease in Caenorhabditis elegans and the SH-SY5Y Cell Line. International Journal of Molecular Sciences. 2020; 21 (12):4455.
Chicago/Turabian StyleRong-Tzong Tsai; Chia-Wen Tsai; Shih-Ping Liu; Jia-Xin Gao; Yun-Hua Kuo; Pei-Min Chao; Huey-Shan Hung; Woei-Cherng Shyu; Shinn-Zong Lin; Ru-Huei Fu. 2020. "Maackiain Ameliorates 6-Hydroxydopamine and SNCA Pathologies by Modulating the PINK1/Parkin Pathway in Models of Parkinson’s Disease in Caenorhabditis elegans and the SH-SY5Y Cell Line." International Journal of Molecular Sciences 21, no. 12: 4455.
Leptin (LEP) regulates glucose metabolism and energy storage in the body. Osteoarthritis (OA) is associated with the upregulation of serum LEP. LEP promoter methylation is associated with obesity. So far, few studies have explored the association of BMI and OA with LEP methylation. We assessed the interaction between body mass index (BMI) and OA on LEP promoter methylation. Data of 1114 participants comprising 583 men and 558 women, aged 30–70 years were retrieved from the Taiwan Biobank Database (2008–2015). Osteoarthritis was self-reported and cases were those who reported having ever been clinically diagnosed with osteoarthritis. BMI was categorized into underweight, normal weight, overweight, and obesity. The mean LEP promoter methylation level in individuals with osteoarthritis was 0.5509 ± 0.00437 and 0.5375 ± 0.00101 in those without osteoarthritis. The interaction between osteoarthritis and BMI on LEP promoter methylation was significant (p-value = 0.0180). With normal BMI as the reference, the mean LEP promoter methylation level was significantly higher in obese osteoarthritic individuals (β = 0.03696, p-value = 0.0187). However, there was no significant association between BMI and LEP promoter methylation in individuals without osteoarthritis, regardless of BMI. In conclusion, only obesity was significantly associated with LEP promoter methylation (higher levels) specifically in osteoarthritic patients.
Tzi-Peng Yang; Hsiao-Mei Chen; Chao-Chin Hu; Li-Yuan Chen; Fen-Fen Shih; Disline Manli Tantoh; Kuan-Jung Lee; Yi-Chia Liaw; Rong-Tzong Tsai; Yung-Po Liaw. Interaction of Osteoarthritis and BMI on Leptin Promoter Methylation in Taiwanese Adults. International Journal of Molecular Sciences 2019, 21, 123 .
AMA StyleTzi-Peng Yang, Hsiao-Mei Chen, Chao-Chin Hu, Li-Yuan Chen, Fen-Fen Shih, Disline Manli Tantoh, Kuan-Jung Lee, Yi-Chia Liaw, Rong-Tzong Tsai, Yung-Po Liaw. Interaction of Osteoarthritis and BMI on Leptin Promoter Methylation in Taiwanese Adults. International Journal of Molecular Sciences. 2019; 21 (1):123.
Chicago/Turabian StyleTzi-Peng Yang; Hsiao-Mei Chen; Chao-Chin Hu; Li-Yuan Chen; Fen-Fen Shih; Disline Manli Tantoh; Kuan-Jung Lee; Yi-Chia Liaw; Rong-Tzong Tsai; Yung-Po Liaw. 2019. "Interaction of Osteoarthritis and BMI on Leptin Promoter Methylation in Taiwanese Adults." International Journal of Molecular Sciences 21, no. 1: 123.
Aflatoxins are carcinogenic secondary metabolites of fungi that contaminate many staple crops and foods. Aflatoxin contamination is a worldwide problem, especially in developing countries, posing health hazards, e.g., causing aflatoxicosis and hepatocellular carcinoma, and even death. Biological solutions for aflatoxin detoxification are environmentally friendly and a cheaper alternative than chemical methods. The aims of the current study were to investigate: (1) the ability of MSMEG_5998, an aflatoxin-degrading F420H2-dependent reductase from Mycobacterium smegmatis, to degrade aflatoxin B1 (AFB1) and reduce AFB1-caused damage in HepG2 cell culture model; and (2) whether a thioredoxin (Trx) linkage of MSMEG_5998 enhanced the enzyme activity. We show that Trx-linked MSMEG_5998 degraded 63% AFB1 and native MSMEG_5998 degraded 31% after 4 h at 22 °C, indicating that the Trx-linked enzyme had a better AFB1-degrading ability. In a HepG2 cell culture model, Trx-linked MSMEG_5998 reduced DNA damage and p53-mediated apoptosis caused by AFB1 to a greater extent than the native enzyme. These findings suggest that Trx-linked MSMEG_5998 could potentially be developed to protect the liver from AFB1 damage, or as a candidate protein to reduce AFB1-related toxicity in animals.
Che-Hsing Li; Wei-Yang Li; I-Ning Hsu; Yung-Yu Liao; Chi-Ya Yang; Matthew C. Taylor; Yu-Fan Liu; Wei-Hao Huang; Hsiang-Hua Chang; Ho-Lo Huang; Shao-Chi Lo; Ting-Yu Lin; Wei-Che Sun; Ya-Yi Chuang; Yu-Chieh Yang; Ru-Huei Fu; Rong-Tzong Tsai. Recombinant Aflatoxin-Degrading F420H2-Dependent Reductase from Mycobacterium smegmatis Protects Mammalian Cells from Aflatoxin Toxicity. Toxins 2019, 11, 259 .
AMA StyleChe-Hsing Li, Wei-Yang Li, I-Ning Hsu, Yung-Yu Liao, Chi-Ya Yang, Matthew C. Taylor, Yu-Fan Liu, Wei-Hao Huang, Hsiang-Hua Chang, Ho-Lo Huang, Shao-Chi Lo, Ting-Yu Lin, Wei-Che Sun, Ya-Yi Chuang, Yu-Chieh Yang, Ru-Huei Fu, Rong-Tzong Tsai. Recombinant Aflatoxin-Degrading F420H2-Dependent Reductase from Mycobacterium smegmatis Protects Mammalian Cells from Aflatoxin Toxicity. Toxins. 2019; 11 (5):259.
Chicago/Turabian StyleChe-Hsing Li; Wei-Yang Li; I-Ning Hsu; Yung-Yu Liao; Chi-Ya Yang; Matthew C. Taylor; Yu-Fan Liu; Wei-Hao Huang; Hsiang-Hua Chang; Ho-Lo Huang; Shao-Chi Lo; Ting-Yu Lin; Wei-Che Sun; Ya-Yi Chuang; Yu-Chieh Yang; Ru-Huei Fu; Rong-Tzong Tsai. 2019. "Recombinant Aflatoxin-Degrading F420H2-Dependent Reductase from Mycobacterium smegmatis Protects Mammalian Cells from Aflatoxin Toxicity." Toxins 11, no. 5: 259.
Parkinson's disease (PD) is the second most common degenerative disorder of the central nervous system in the elderly.It is characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta, as well as by motor dysfunction. Although the causes of PD are not well understood, aggregation of α-synuclein (α-syn) in neurons contributes to this disease. Currently, therapeutics for PD provide satisfactory symptom relief, but not a cure. Treatment strategies include attempts to identify new drugs that will prevent or arrest the progressive course of PD by correcting disease-specific pathogenic process. Betulin is derived from the bark of birch trees, and possesses anti-cancer, antimicrobial, and antiinflammatory properties. The aim of the present study was to evaluate the potential for betulin to ameliorate PD features in Caenorhabditis elegans (C. elegans) models. We demonstrated that betulin diminished α-syn accumulation in the transgenic C. elegans model. Betulin also reduced 6-hydroxydopamine-induced dopaminergic neuron degeneration, reduced foodsensing behavioral abnormalities, and reversed life-span decreases in a pharmacological C. elegans model. Moreover, we found that enhancement of proteasomes activity by promoting rpn1 expression and down-regulation of the apoptosis pathway gene, egl-1, may be the molecular mechanism for betulin-mediated protection against PD pathology. Together, these findings support betulin as a possible treatment for PD and encourage further investigations of betulin as an anti-neurodegenerative agent.
Chia-Wen Tsai; Rong-Tzong Tsai; Shih-Ping Liu; Chang-Shi Chen; Min-Chen Tsai; Shao-Hsuan Chien; Huey-Shan Hung; Shinn-Zong Lin; Woei-Cherng Shyu; Ru-Huei Fu. Neuroprotective Effects of Betulin in Pharmacological and Transgenic C. elegans Models of Parkinson’s Disease. Cell Transplantation 2017, 1 .
AMA StyleChia-Wen Tsai, Rong-Tzong Tsai, Shih-Ping Liu, Chang-Shi Chen, Min-Chen Tsai, Shao-Hsuan Chien, Huey-Shan Hung, Shinn-Zong Lin, Woei-Cherng Shyu, Ru-Huei Fu. Neuroprotective Effects of Betulin in Pharmacological and Transgenic C. elegans Models of Parkinson’s Disease. Cell Transplantation. 2017; ():1.
Chicago/Turabian StyleChia-Wen Tsai; Rong-Tzong Tsai; Shih-Ping Liu; Chang-Shi Chen; Min-Chen Tsai; Shao-Hsuan Chien; Huey-Shan Hung; Shinn-Zong Lin; Woei-Cherng Shyu; Ru-Huei Fu. 2017. "Neuroprotective Effects of Betulin in Pharmacological and Transgenic C. elegans Models of Parkinson’s Disease." Cell Transplantation , no. : 1.
The peroxisome is a single membrane-bound organelle in eukaryotic cells involved in lipid metabolism, including β-oxidation of fatty acids. The human genetic disorder X-linked adrenoleukodystrophy (X-ALD) is caused by mutations in the ABCD1 gene (encoding ALDP, a peroxisomal half ATP-binding cassette [ABC] transporter). This disease is characterized by defective peroxisomal β-oxidation and a large accumulation of very long-chain fatty acids in brain white matter, adrenal cortex, and testis. ALDP forms a homodimer proposed to be the functional transporter, whereas the peroxisomal transporter in yeast is a heterodimer comprising two half ABC transporters, Pxa1p and Pxa2p, both orthologs of human ALDP. While the carboxyl-terminal domain of ALDP is engaged in dimerization, it remains unknown whether the same region is involved in the interaction between Pxa1p and Pxa2p. Using a yeast two-hybrid assay, we found that the carboxyl-terminal region (CT) of Pxa2p, but not of Pxa1p, is required for their interaction. Further analysis indicated that the central part of the CT (designated CT2) of Pxa2p was indispensable for its interaction with the carboxyl terminally truncated Pxa1_NBD. An interaction between the CT of Pxa2p and Pxa1_NBD was not detected, but could be identified in the presence of Pxa2_NBD-CT1. A single mutation of two conserved residues (aligned with X-ALD-associated mutations at the same positions in ALDP) in the CT2 of the Pxa2_NBD-CT protein impaired its interaction with Pxa1_NBD or Pxa1_NBD-CT, resulting in a mutant protein that exhibited a proteinase K digestion profile different from that of the wild-type protein. Functional analysis of these mutant proteins on oleate plates indicated that they were defective in transporter function. The CT of Pxa2p is involved in its interaction with Pxa1p and in transporter function. This concept may be applied to human ALDP studies, helping to establish the pathological mechanism for CT-related X-ALD disease.
Cheng-Yi Chuang; Ling-Yun Chen; Ru-Huei Fu; Shih-Ming Chen; Ming-Hua Ho; Jie-Mau Huang; Chia-Chi Hsu; Chien-Cheng Wang; Meng-Shian Chen; Rong-Tzong Tsai. Involvement of the Carboxyl-Terminal Region of the Yeast Peroxisomal Half ABC Transporter Pxa2p in Its Interaction with Pxa1p and in Transporter Function. PLOS ONE 2014, 9, e104892 .
AMA StyleCheng-Yi Chuang, Ling-Yun Chen, Ru-Huei Fu, Shih-Ming Chen, Ming-Hua Ho, Jie-Mau Huang, Chia-Chi Hsu, Chien-Cheng Wang, Meng-Shian Chen, Rong-Tzong Tsai. Involvement of the Carboxyl-Terminal Region of the Yeast Peroxisomal Half ABC Transporter Pxa2p in Its Interaction with Pxa1p and in Transporter Function. PLOS ONE. 2014; 9 (8):e104892.
Chicago/Turabian StyleCheng-Yi Chuang; Ling-Yun Chen; Ru-Huei Fu; Shih-Ming Chen; Ming-Hua Ho; Jie-Mau Huang; Chia-Chi Hsu; Chien-Cheng Wang; Meng-Shian Chen; Rong-Tzong Tsai. 2014. "Involvement of the Carboxyl-Terminal Region of the Yeast Peroxisomal Half ABC Transporter Pxa2p in Its Interaction with Pxa1p and in Transporter Function." PLOS ONE 9, no. 8: e104892.