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学科主题: 公共卫生
题名:
Aldo-keto reductase 1 family B7 is the gene induced in response to oxidative stress in the livers of Long-Evans Cinnamon rats
作者: Jia, Guang; Takahashi, Ryoya; Zhang, Zhiping; Tsuji, Yoshiaki; Sone, Hideko
关键词: AKR1B7 ; oxidative stress ; oligonucleotide array ; realtime PCR ; Long Evans Cinnamon rat
刊名: INTERNATIONAL JOURNAL OF ONCOLOGY
发表日期: 2006-10-01
卷: 29, 期:4, 页:829-838
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: NF-KAPPA-B ; MOUSE VAS-DEFERENS ; LEC RATS ; HEPATOCELLULAR-CARCINOMA ; TRANSCRIPTIONAL REGULATION ; ADRENOCORTICAL-CELLS ; PLASMA ANTIOXIDANTS ; LIPID-PEROXIDATION ; HYDROXYL RADICALS ; HEME OXYGENASE
英文摘要:

The Long-Evans Cinnamon (LEC) rat strain (Atp7b m/m), which accumulates copper in the liver due to mutations in the Atp7b gene, is a useful model for investigating the relationship between oxidative stress and hepatocarcinogenesis. To determine the effect of this mutation on oxidative stress marker genes, we performed oligonucleotide array analysis (Affymetrix), and compared the results in Atp7b m/m rats with those of a sibling line with the Atp7b w/w genotype. We focused our studies on the expression of the aldo-keto reductase I family B7 (AKR1B7)-like protein gene, since this gene codes for reductase enzymes involved in the detoxification of oxidizing compounds (e.g., aldehydes) and was differentially expressed in Atp7b m/m and Atp7b w/w rat liver. Akr1B7 mRNA expression was significantly increased in comparison with the expression of 4 other known oxidative stress responsive genes, haem-oxygenase-1 (HO-1), thioredoxin (Trx), aldehyde reductase (AKR1A1), and glucose-6-phosphate dehydrogenase (G6PDH). By searching binding motifs, five nuclear factor kappa B (NF-KB) binding sites were located in the 5′-upstream region of the Akr1b7 gene. Transient co-transfection with both I-kBa and the Akr1b7 6 kb promoter (p6.0-AKR-Luc) inhibited luciferase activity of p6.0-AKR-Luc in HepG2 cells. Cuprous ion however did not affect the transcription activity induced by p6.0-AKR-Luc. Gel-shift assay showed that the DNA binding activity of NF-KB increased in the livers of LEC rats, suggesting that the oxidative stress is mediated through NF-KB. The results indicate conclusively that in LEC rat liver, Akr1b7 might be up-regulated by oxidative stress mediated through NF-KB, but not that mediated directly by copper.

语种: 英语
WOS记录号: WOS:000240803900007
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/67848
Appears in Collections:北京大学公共卫生学院_期刊论文

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作者单位: 1.Toho Univ, Fac Pharmaceut Sci, Biochem Lab, Chiba 2748510, Japan
2.Natl Inst Environm Studies, Hlth Effects Res Team, Tsukuba, Ibaraki 3058506, Japan
3.Peking Univ, Sch Publ Hlth, Dept Occupat & Environm Hlth Sci, Beijing 100083, Peoples R China
4.Natl Inst Environm Hlth Sci, Lab Reprod & Dev, Res Triangle Pk, NC 27709 USA
5.N Carolina State Univ, Dept Environm & Mol Toxicol, Raleigh, NC 27695 USA

Recommended Citation:
Jia, Guang,Takahashi, Ryoya,Zhang, Zhiping,et al. Aldo-keto reductase 1 family B7 is the gene induced in response to oxidative stress in the livers of Long-Evans Cinnamon rats[J]. INTERNATIONAL JOURNAL OF ONCOLOGY,2006,29(4):829-838.
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