Response of Vascular Cells to Oxidative Stress

血管细胞对氧化应激的反应

• 批准号: 10044234
• 负责人: BANNAI Shiro
• 金额: $ 4.99万
• 依托单位: University of Tsukuba
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-10044234/
• 关键词: oxidative stress; stress protein; macrophages; vascular smooth muscle cell; amino acid transporter; heme oxygenase; glutathione; atherosclerosis; アミノ酸トシンスポーター; ストレス タンパク質; 一酸化窒素; 定密度リポタンパク

We have investigated the response to oxidative stress in vascular cells and tissues.The results are as follows :1. Macrophages are thought to be able to oxidize low-density lipoprotein (LDL).Oxidation of LDL is probably coupled with reduction of ferric ion. We have obtained evidence showing that activated macrophages can reduce ferric ion though resting macrophages cannot.2. We have examined the effects of oxidized LDL and the antioxidant vitamin C in human arterial smooth muscle cells. These cells exhibit typical response to oxidized LDL but pretreatment with vitamin C abolishes the response in a dosedependent manner.3. We have obtained evidence showing the high expression of heme oxygenase 1 in atherosclerotic region, particularly in macrophages.4. cDNA for cystine/glutamate transporter has been cloned. Two proteins, 4F2hc and xCT, constitute the transporter. xCT is a novel protein with 12 transmembrane domains. The activity of the transporter is important in maintaining intracellular glutathione level and hence in tolerance to oxidative stress. The 5'-flanking region of xCT gene has been analyzed and the regulation of the transcription by the transcription factor Nrf2 has been found.5. Induction of peroxiredoxin I by oxidative stress has been examined and the transcriptional regulation similar to that of cystine transporter protein xCT has been found.

我们研究了血管细胞和组织对氧化应激的反应。研究结果如下：1。巨噬细胞被认为能够氧化低密度脂蛋白（LDL）。低密度脂蛋白的氧化可能伴随着铁离子的还原。我们有证据表明激活的巨噬细胞可以减少铁离子，而静止的巨噬细胞则不能。我们研究了氧化LDL和抗氧化剂维生素C在人动脉平滑肌细胞中的作用。这些细胞对氧化LDL表现出典型的反应，但用维生素C预处理以剂量依赖的方式消除了这种反应。我们已经获得证据表明血红素加氧酶1在动脉粥样硬化区，特别是巨噬细胞中高表达。已克隆出胱氨酸/谷氨酸转运体cDNA。两种蛋白，4F2hc和xCT，构成转运蛋白。xCT是一种具有12个跨膜结构域的新型蛋白。转运体的活性在维持细胞内谷胱甘肽水平和对氧化应激的耐受性方面是重要的。分析了xCT基因的5'-侧翼区域，发现转录因子Nrf2对转录的调控作用。研究了氧化应激对过氧化物还蛋白I的诱导作用，发现其转录调控与胱氨酸转运蛋白xCT相似。

项目成果

Tachi,Y.: "High concentration of glucose causes impairment of the function of the glutathione redox cycle in huamn vascular smooth muscle cells."FEBS Lett.. 421. 19-22 (1998)

Tachi,Y.：“高浓度的葡萄糖会损害人类血管平滑肌细胞中谷胱甘肽氧化还原循环的功能。”FEBS Lett.. 421. 19-22 (1998)

Siow, R.C.M., Sato H., Leake, D.S., Ishii, T., Bannai, S., and Mann G.E.: "Induction of antioxidant stress proteins in vascular endothelial and smooth muscle cells : protective action of vitamin C against atherogenic lipoproteins."Free Rad.Res.. 31. 309-3

Siow, R.C.M.、Sato H.、Leake, D.S.、Ishii, T.、Bannai, S. 和 Mann G.E.：“血管内皮和平滑肌细胞中抗氧化应激蛋白的诱导：维生素 C 对致动脉粥样硬化脂蛋白的保护作用。”

Ishii, T., Itoh, K., Sato, H., and Bannai, S.: "Oxidative stress-inducible proteins in macrophages."Free Rad.Res.. 31. 351-355 (1999)

Ishii, T.、Itoh, K.、Sato, H. 和 Bannai, S.：“巨噬细胞中的氧化应激诱导蛋白”。Free Rad.Res.. 31. 351-355 (1999)

Mizusawa, H., Ishii, T., and Bannai, S.: "Peroxiredoxin I (macrophage 23kDa stress protein) is highly and widely expressed in the rat nervous system."Neurosci.Lett.. 283. 57-60 (2000)

Mizusawa, H.、Ishii, T. 和 Bannai, S.：“Peroxiredoxin I（巨噬细胞 23kDa 应激蛋白）在大鼠神经系统中高度且广泛表达。”Neurosci.Lett.. 283. 57-60 (2000)

Hong, Y., Suzuki, S., Yatoh, S., Mizutani, M., Nakajima, T., Bannai, S., Sato, H., Soma, M., Okuda, Y., and Yamada, N.: "Effect of hypoxia on nitric oxide production and its synthase gene expression in rat smooth muscle cells."Biochem.Biophys.Res.Commun..

Hong, Y.、铃木, S.、矢藤 S.、水谷 M.、中岛 T.、班内 S.、佐藤 H.、相马 M.、奥田 Y. 和山田 N.