TY - JOUR
T1 - Nickel-induced 1,4-α-glucan branching enzyme 1 up-regulation via the hypoxic signaling pathway
AU - Zhao, Jianhua
AU - Chen, Haobin
AU - Davidson, Todd
AU - Kluz, Thomas
AU - Zhang, Qunwei
AU - Costa, Max
PY - 2004/5/1
Y1 - 2004/5/1
N2 - Using the mouse Affymetrix gene chip, we found that 1,4-α-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-1α (HIF-1α) was involved in the up-regulation of this gene. Experiments using HIF-1α +/+ and HIF-1α -/- mouse cells demonstrated this gene was up-regulated through a HIF-1α-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.
AB - Using the mouse Affymetrix gene chip, we found that 1,4-α-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-1α (HIF-1α) was involved in the up-regulation of this gene. Experiments using HIF-1α +/+ and HIF-1α -/- mouse cells demonstrated this gene was up-regulated through a HIF-1α-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.
KW - GBE1
KW - HIF-1α
KW - Nickel
UR - http://www.scopus.com/inward/record.url?scp=1942535773&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2004.01.012
DO - 10.1016/j.taap.2004.01.012
M3 - Article
C2 - 15094311
AN - SCOPUS:1942535773
SN - 0041-008X
VL - 196
SP - 404
EP - 409
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
IS - 3
ER -