镍通过缺氧信号通路诱导1,4-α-葡聚糖分支酶1上调。

Nickel-induced 1,4-alpha-glucan branching enzyme 1 up-regulation via the hypoxic signaling pathway.

作者信息

Zhao Jianhua, Chen Haobin, Davidson Todd, Kluz Thomas, Zhang Qunwei, Costa Max

机构信息

Department of Environmental Medicine, New York University School of Medicine, 57 Old Forge Road, Tuxedo, NY 10987, USA.

出版信息

Toxicol Appl Pharmacol. 2004 May 1;196(3):404-9. doi: 10.1016/j.taap.2004.01.012.

DOI:10.1016/j.taap.2004.01.012

PMID:15094311

Abstract

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.

摘要

使用小鼠Affymetrix基因芯片，我们发现1,4-α-葡聚糖分支酶1（GBE1）是镍暴露后上调最为显著的基因之一。该结果在两种小鼠细胞系、四种小鼠组织以及三种人类细胞系中通过Northern印迹法得到了证实。我们进一步发现，该基因在钴、缺氧、铁螯合剂（去铁胺，或DFO）以及脯氨酰羟化酶（PH）抑制剂（二甲基草酰甘氨酸，DMOG）作用下也会上调，这表明缺氧诱导因子-1α（HIF-1α）参与了该基因的上调过程。使用HIF-1α +/+和HIF-1α -/-小鼠细胞进行的实验表明，该基因是通过HIF-1α依赖的缺氧信号通路而上调的。由于缺氧信号通路被认为在癌症发生和发展过程中起着重要作用，因此研究受该通路调控的基因具有重要意义。