title: The role of NAD(+)-dependent isocitrate dehydrogenase 3 subunit α in AFB1 induced liver lesion.
abstract: Aflatoxin B1 (AFB1) is a potent hepatocarcinogen that causes carcinogenesis in many animal species. In previous study, we found that isocitrate dehydrogenase 3α subunit (IDH3α) was upregulated in AFB1-induced carcinogenesis process. In this study, the sequences of IDH3α from various species were compared and the protein expression levels in different organs were examined, and the results showed that IDH3α was a widely distributed protein and shared highly conserved sequence in various species. In the same time, IDH3α was demonstrated to accumulate in a dose-dependent manner induced by AFB1 in cells, and was also up-regulated in the process of AFB1-induced liver lesion. Similar results were observed when H2O2 was used to replace AFB1. Over-expression of IDH3α increased the phosphorylation level of Akt (Protein kinase B) and neutralized the cellular toxicity induced by AFB1 or H2O2 and apoptosis induced by AFB1, while the reduced expression of IDH3α by siRNA decreased the phosphorylation, indicating that IDH3α played important roles in oxidative stress-induced PI3K/Akt pathway. Overall, the results suggested that AFB1 treatment could increase the expression of IDH3α, and the activated PI3K/Akt pathway by IDH3α eventually neutralized the apoptosis induced by AFB1.
authors.affiliation: Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, The Ministry of Education Key Laboratory of Biopesticide and Chemical Biology, and School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
authors.forename: Chi
authors.initials: C
authors.lastname: Yang
authors.affiliation: Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, The Ministry of Education Key Laboratory of Biopesticide and Chemical Biology, and School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
authors.forename: Jue
authors.initials: J
authors.lastname: Fan
authors.affiliation: Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, The Ministry of Education Key Laboratory of Biopesticide and Chemical Biology, and School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
authors.forename: Zhenhong
authors.initials: Z
authors.lastname: Zhuang
authors.affiliation: Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, The Ministry of Education Key Laboratory of Biopesticide and Chemical Biology, and School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Fang
authors.affiliation: Department of Biochemistry, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Pathogenic Fungi and Mycotoxins of Fujian Province, The Ministry of Education Key Laboratory of Biopesticide and Chemical Biology, and School of Life Sciences, Fujian Agriculture and Forestry University, Fuzhou 350002, China. Electronic address: wshyyl@sina.com.
authors.forename: Shihua
authors.initials: S
authors.lastname: Wang
mesh_terms: D016604:Aflatoxin B1 / Q000633:toxicity*; D000818:Animals; D017304:Annexin A5; D001483:Base Sequence; D015153:Blotting, Western; D002273:Carcinogens / Q000633:toxicity*; D002478:Cells, Cultured; D056486:Chemical and Drug Induced Liver Injury / Q000201:enzymology*; D004591:Electrophoresis, Polyacrylamide Gel; D016650:Fluorescein-5-isothiocyanate; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007521:Isocitrate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D051058:Oncogene Protein v-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013045:Species Specificity
chemical_list: D017304:Annexin A5; D002273:Carcinogens; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D016604:Aflatoxin B1; D006861:Hydrogen Peroxide; D007521:Isocitrate Dehydrogenase; D051058:Oncogene Protein v-akt; D016650:Fluorescein-5-isothiocyanate
keywords: ALB; ALT; AST; Aflatoxin B(1); DBIL; HCC; IDH; Isocitrate dehydrogenase 3α; LDH; Protein kinase B; ROS; Reactive oxygen species; TBIL; TP; alanine aminotransferase; albumin; aspartate amino-transferase; direct bilirubin; hepatocellular carcinoma; isocitrate dehydrogenase; lactate dehydrogenase; reactive oxygen species; total bilirubin; total protein