Identification of oxidative stress related genes and transcription factors in vascular tissues
血管组织中氧化应激相关基因和转录因子的鉴定
基本信息
- 批准号:11671112
- 负责人:
- 金额:$ 1.98万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:1999
- 资助国家:日本
- 起止时间:1999 至 2001
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
To evaluate abnormalities in the mitochondrial transcription factor A (mtTFA) function as a cause of mitochondrial dysfunction in diabetes, we measured the mRNA contents of the proteins consisting of the mitochondrial respiratory chain as well as transcriptional and translational activities in the mitochondria isolated from controls and streptozotocin-induced diabetic rat hearts. Using Northern blot analysis, we found the 40 % reduced mRNA contents of mitochondrial-encoded cytochrome b and ATP synthase subunit 6 in diabetic rat hearts compared with control rats (P < 0.05). These abnormalities were completely recovered by insulin treatment. Furthermore, the mitochondrial activities of transcription and translation were decreased significantly in mitochondria isolated from diabetic rats by 60 % (P < 0.01) and by 71 % (P < 0.01), respectively compared with control rats. The insulin treatment also completely normalized these abnormalities in diabetic rats. Consistently, gel retardation assay showed a reduced binding of mtTFA to the D-loop of mitochondrial DNA in diabetic rats, although there was no difference in the mtTFA mRNA and protein contents between the two groups. Based on these findings, a reduced binding activity of mtTFA to the D-loop region in the hearts of diabetic rats may contribute to the decreased mitochondrial protein synthesis.
为了评估线粒体转录因子A(mtTFA)功能异常作为糖尿病线粒体功能障碍的原因,我们测量了由线粒体呼吸链组成的蛋白质的mRNA含量以及从对照组和链脲佐菌素诱导的糖尿病大鼠心脏中分离的线粒体中的转录和翻译活性。北方杂交结果显示,糖尿病大鼠心肌细胞色素B和ATP合成酶亚基6的mRNA含量较对照组降低40%(P < 0.05)。这些异常通过胰岛素治疗完全恢复。糖尿病大鼠线粒体转录和翻译活性较对照组分别降低60%(P < 0.01)和71%(P < 0.01)。胰岛素治疗也使糖尿病大鼠的这些异常完全正常化。凝胶阻滞实验显示,糖尿病大鼠线粒体DNA D环与mtTFA的结合减少,但两组mtTFA的mRNA和蛋白含量无明显差异。基于这些发现,糖尿病大鼠心脏中mtTFA与D-环区域的结合活性降低可能有助于线粒体蛋白质合成减少。
项目成果
期刊论文数量(10)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Kazuya Shinozaki et al.: "Oral administration of tetrahydrobiopterin prevents endothelial dysfunction and vascular oxidative stress in the aorta of insulin-resistant rats"Circulation Research. 87. 566-573 (2000)
Kazuya Shinozaki 等人:“口服四氢生物蝶呤可预防胰岛素抵抗大鼠主动脉内皮功能障碍和血管氧化应激”循环研究。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Atsunori Kashiwagi et al.: "Endothelium-specific activation of NADPH/NADH oxidases in aortas of exogenousely hyperinsulinemic rats"American Journal of Physiology. 277. E976-E983 (1999)
Atsunori Kashiwagi 等人:“外源性高胰岛素血症大鼠主动脉中 NADPH/NADH 氧化酶的内皮特异性激活”美国生理学杂志。
- DOI:
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- 影响因子:0
- 作者:
- 通讯作者:
Shinozaki K,Kashiwagi A,Nishio Y et al.: "Abnormal biopterin metabolism is a major cause of impaired endothelium-dependent relaxation through nitric oxide/O2-imbalance in insulin-resistant rat aorta"Diabetes. 48. 2437-2445 (1999)
Shinozaki K、Kashiwagi A、Nishio Y 等人:“生物蝶呤代谢异常是胰岛素抵抗大鼠主动脉中一氧化氮/O2 失衡导致内皮依赖性舒张受损的主要原因”糖尿病。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Kazuya Shinozaki et al.: "Abnormal biopterin metabolism is a major cause of impaired endothelium-dependent relaxation through nitric oxide/O2-imbalance in insulin-resistat rat aorta"Diabetes. 48. 2437-2445 (1999)
Kazuya Shinozaki 等人:“生物蝶呤代谢异常是胰岛素抵抗大鼠主动脉中一氧化氮/氧气失衡导致内皮依赖性舒张受损的主要原因”糖尿病。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
S. Fujirio, K. Kato, A. Mori: "Experimental Studies for Application of Fixed Lung as an Oxygenator"Report of Research project, Grant-in-Aid for scientific Research. No.06671336. (1996)
S. Fujirio、K. Kato、A. Mori:“固定肺作为氧合器应用的实验研究”研究项目报告,科学研究补助金。
- DOI:
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- 影响因子:0
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{{ truncateString('NISHIO Yoshihiko', 18)}}的其他基金
The effects of omega-3 PUFA on vascular function
omega-3 PUFA 对血管功能的影响
- 批准号:
23591336 - 财政年份:2011
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification and characterization of a new factor regulating SREBP-1c gene in liver.
肝脏中 SREBP-1c 基因调节新因子的鉴定和表征。
- 批准号:
20591058 - 财政年份:2008
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Elucidation of the mechanism for the activation of transcription factors and gene response in the aorta of the Postprandial state of rata
阐明大鼠餐后状态主动脉转录因子激活和基因反应的机制
- 批准号:
18590981 - 财政年份:2006
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of the inhibitory factor for the transcription of inflammatory genes in vascular smooth muscle cells
血管平滑肌细胞炎症基因转录抑制因子的鉴定
- 批准号:
16590877 - 财政年份:2004
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
A novel effect of insulin on vascular smooth muscle cells through the transcriptional regulation ?the meaning of the activation of C/EBP
胰岛素通过转录调控对血管平滑肌细胞的新作用——C/EBP激活的意义
- 批准号:
14571090 - 财政年份:2002
- 资助金额:
$ 1.98万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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