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Ye Huang, Xiuli Yi,
Zhe Jian,
Chao Wei,
Shuli Li,
Chuan Cai,
Ping Zhang,
Kai Li,
Sen Guo,
Ling Liu,
Qiong Shi,
Tianwen Gao,
Chunying Li
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ABSTRACT: Recent evidence indicates that oxidative stress and genetic factors play an important role in the pathogenesis of vitiligo. SNPs in miRNAs involved in oxidative stress could potentially influence the development of vitiligo. In this case-control study, we investigated the association of a functional SNP of rs11614913 in miR-196a-2 with risk of vitiligo. A significantly lower risk of vitiligo was associated with the rs11614913 miR-196a-2 CC genotype (adjusted OR, 0.77; CI, 0.60-0.98). In addition, TYRP1 gene expression was considerably down-regulated by the rs11614913 C allele in miR-196a-2, which lowered the levels of intracellular reactive oxygen species (ROS) and reduced the proportion of early apoptosis in human melanocytes in response to H(2) O(2) treatment. Our data suggest that the rs11614913 C allele in miR-196a-2 confers potential protection against oxidative effects on human melanocytes through the modulation of the target gene, TYRP1, which may account for the decreased risk of vitiligo in this study population. © 2013 John Wiley & Sons A/S.
Pigment Cell & Melanoma Research 02/2013; · 5.06 Impact Factor
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Chao Wei,
Zhe Jian,
Lin Wang,
Huini Qiang,
Qiong Shi,
Sen Guo,
Kai Li,
Ye Huang,
Ling Liu,
Qiang Li,
Qi Luan, Xiuli Yi,
Xia Li,
Gang Wang,
Tianwen Gao,
Chunying Li
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ABSTRACT: Vitiligo is an acquired depigmentation disorder, and reactive oxygen species play an important role in melanocyte damage. Base excision repair (BER) is the major pathway responsible for removing reactive oxygen species-induced DNA damage, in which APE1, ADPRT, and XRCC1 play key roles. To investigate the association between genetic variations of these genes and the risk of vitiligo in Chinese populations, we genotyped APE1-Asp148Glu, ADPRT-Val762Ala, and XRCC1-Arg399Gln polymorphisms and measured serum 8-OHdG levels in a hospital-based case-control study. We found that a significantly increased risk of vitiligo was associated with the APE1 Asp/Glu [adjusted odds ratio (OR), 1.24; 95% confidence interval (CI), 1.02-1.52] and Glu/Glu genotypes (adjusted OR, 1.48; 95%CI, 1.13-1.93), compared with the APE1 Asp/Asp genotype, while no vitiligo risk was associated with genotypes of ADPRT-Val762Ala or XRCC1-Arg399Gln. Furthermore, serum 8-OHdG levels were elevated in the APE1-148Gluallelecarriers (Asp/Glu+Glu/Glu), in an allele dose-response manner, with the risk of vitiligo (P(trend)<0.05). In addition, we found that the APE1-148Glu variant increased the 8-OHdG levels of cultured human melanocytes treated with H(2)O(2), without any impact on the endonuclease activity. These data suggest that the APE1-Asp148Glu polymorphism aggravates oxidative stress in human melanocytes and contributes to genetic predisposition to vitiligo in Chinese people.
Free radical biology & medicine 01/2013; · 5.42 Impact Factor
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Bangmin Liu,
Zhe Jian,
Qiang Li,
Kai Li,
Zhiyong Wang,
Ling Liu,
Lingzhen Tang, Xiuli Yi,
Hua Wang,
Chunying Li,
Tianwen Gao
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ABSTRACT: The removal of H(2)O(2) by antioxidants has been proven to be beneficial to patients with vitiligo. Baicalein (5,6,7-trihydroxyflavone; BE) has antioxidant activity and has been used in vitiligo therapy in Chinese traditional medicine. In this study, we investigated the potential protective effect and mechanisms of BE against H(2)O(2)-induced apoptosis in human melanocytes. Melanocytes from the PIG1 cell line were pretreated with different concentrations of BE for 1 h, followed by exposure to 1.0 mM H(2)O(2) for 24 h. Cell apoptosis, reactive oxygen species levels, and mitochondrial membrane potentials were evaluated by flow cytometry, and cell viability was determined by an MTT assay. The expressions of Bax, Bcl-2, caspase-3, total and phosphorylated ERKs, and p38 MAPK were assayed by Western blot to investigate the possible molecular mechanisms. Our results showed that BE significantly inhibited H(2)O(2)-induced apoptosis, intracellular reactive oxygen species generation, and changes in the mitochondrial membrane potential. It also reduced the Bax/Bcl-2 ratio, the release of cytochrome c, the activation of caspase-3, and the phosphorylation of p38 MAPK in a concentration-dependent manner. The results demonstrate for the first time that BE exerts a cytoprotective role in H(2)O(2)-induced apoptosis by inhibiting the mitochondria-dependent caspase activation and p38 MAPK pathway.
Free radical biology & medicine 05/2012; 53(2):183-93. · 5.42 Impact Factor
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Qiang Li,
Yajie Lv,
Chunying Li, Xiuli Yi,
Heather A Long,
Hongjiang Qiao,
Tao Lu,
Qi Luan,
Kai Li,
Xudong Wang,
Gang Wang,
Tianwen Gao
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ABSTRACT: VIT75 is a 75-kDa melanocyte membrane antigen (Ag) that had been observed, but not identified until now. Its immunopathogenic role in vitiligo remains unknown. In this study, serological proteome analysis based on mass spectrometry was employed to identify VIT75. Three disparate 75-, 60-, and 45-kDa proteins on two-dimensional (2D) gel were, respectively, identified as lamin A, tyrosinase-related protein 1, and melanin-concentrating hormone receptor 1. The latter two proteins are well-known Ags. Immunoreactivity analysis showed that the 75-kDa protein displayed on the 2D gel was recognized by human anti-lamin A IgG. Antibody (Ab) reactivity to lamin A was positive in 28.6% of patients' sera. Only 3.1% healthy sera reacted with the lamin A. A total of 91.7% of the positive sera was from the active non-segmental vitiligo (NSV). The positive rate and mean titer of anti-lamin A Ab are higher for NSV with autoimmune disease than for NSV without autoimmune disease. These data demonstrate that VIT75 is lamin A. To our knowledge, this is a previously unreported vitiligo Ag. Anti-lamin A Ab may be a potential marker of NSV with autoimmune disease. The study indicates that the targets of autoantibodies in vitiligo patients can be revealed by serological proteome analysis.
Journal of Investigative Dermatology 11/2010; 131(3):727-34. · 6.31 Impact Factor
