Nickel-induced 1,4-alpha-glucan branching enzyme 1 up-regulation via the hypoxic signaling pathway.
Using the mouse Affymetrix gene chip, we found that 1,4-alpha-glucan branching enzyme 1 (GBE1) was one of the most up-regulated genes following nickel exposure. This result was confirmed by Northern blot in two mouse cell lines, four mouse tissues, and three human cell lines. We further found that this gene was also up-regulated by cobalt, hypoxia, the iron chelator (deferoxamine, or DFO), and the prolyl hydroxylase (PH) inhibitor (dimethyloxalyglycine, DMOG), suggesting that hypoxia inducible factor-1alpha (HIF-1alpha) was involved in the up-regulation of this gene. Experiments using HIF-1alpha +/+ and HIF-1alpha -/- mouse cells demonstrated this gene was up-regulated through a HIF-1alpha-dependent hypoxic signaling pathway. Because the hypoxic signaling pathway is believed to be important in the initiation and progression of carcinogenesis, it is important to study genes regulated by this pathway.
Zhao
Jianhua
J
Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA.
Chen
Haobin
H
Davidson
Todd
T
Kluz
Thomas
T
Zhang
Qunwei
Q
Costa
Max
M
D015061:1,4-alpha-Glucan Branching Enzyme / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D002478:Cells, Cultured; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D000860:Hypoxia / Q000201:enzymology*; D051379:Mice; D009532:Nickel / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
D009532:Nickel; D015061:1,4-alpha-Glucan Branching Enzyme