title: Chromium(VI) causes down regulation of biotinidase in human bronchial epithelial cells by modifications of histone acetylation.
abstract: Hexavalent chromium (Cr(VI)), a commonly used industrial metal, is a well-known mutagen and carcinogen, and occupational exposure can induce a broad spectrum of adverse health effects, including cancers. Although Cr(VI)-induced DNA damage is thought to be the primary mechanism of chromate genotoxicity and mutagenicity, there is an increasing number of reports showing that epigenetic mechanisms of gene regulation might be a central target of Cr(VI) toxicity. Epigenetic changes, such as changes in phosphorylation, altered DNA methylation status, histone acetylation and signaling pathways, have been observed after chromium exposure. Nevertheless, to better demonstrate the roles of epigenetic modifications in Cr(VI)-induced carcinogenesis, more work needs to be carried out. This study is aimed to investigate changes in biotinidase (BTD) and holocarboxylase synthetase (HCS), two major proteins which maintain homeostasis of the newfound epigenetic modification: histone biotinylation, in cells exposed to Cr(VI). The data showed that Cr(VI) decreased BTD expression at the transcriptional level in human bronchial epithelial cells (16HBE). In addition, using the epigenetic modifiers, 5-Aza-2'-deoxycytidine (Aza) and Trichostatin A (TSA), we found that modifications of histone acetylation reversed the inhibition of BTD, suggesting that Cr(VI) may cause down regulation of BTD by modifications of histone acetylation.
authors.affiliation: Department of Toxicology, School of Public Health, Central South University, 110 Xiangya Road, Changsha 410078, Hunan, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xia
authors.forename: Lin-Qing
authors.initials: LQ
authors.lastname: Yang
authors.forename: Hai-Yan
authors.initials: HY
authors.lastname: Huang
authors.forename: Li
authors.initials: L
authors.lastname: Pang
authors.forename: Gong-Hua
authors.initials: GH
authors.lastname: Hu
authors.forename: Qing-Cheng
authors.initials: QC
authors.lastname: Liu
authors.forename: Jian-Hui
authors.initials: JH
authors.lastname: Yuan
authors.forename: Jian-Jun
authors.initials: JJ
authors.lastname: Liu
authors.forename: Yan-Bin
authors.initials: YB
authors.lastname: Xia
authors.forename: Zhi-Xiong
authors.initials: ZX
authors.lastname: Zhuang
mesh_terms: D000107:Acetylation; D043523:Biotinidase / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D015153:Blotting, Western; D001980:Bronchi / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D002274:Carcinogens, Environmental / Q000633:toxicity*; D018929:Cell Culture Techniques; D002460:Cell Line; D002857:Chromium / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004847:Epithelial Cells / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D002274:Carcinogens, Environmental; D006657:Histones; D002857:Chromium; C074702:chromium hexavalent ion; D043523:Biotinidase