THE TARGET GENE FOR PPARα AND PPARγ IN HUVEC

HUVEC 中 PPARα 和 PPARγ 的靶基因

• 批准号: 11671135
• 负责人: INOUE Ikuo
• 金额: $ 1.86万
• 依托单位: Saitama Medical School
• 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 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671135/
• 关键词: peroxisome proliferator-activated receptor α (PPARα); peroxisome proliferator-activated receptor γ (PPARγ); human umbilical vein endothelial cells (HUVEC); nicotine adenine dinucleotide phosphate (NADPH) oxidase; cyclooxygenase-2; interleukin-1β; Cu

We examined the effects of peroxisome proliferator-activated receptor α (PPARα) and PPARγ on the production and expression of inflammatory cytokines and on enzyme expression involving prostaglandin and superoxide production in cultured human umbilical vein endothelial cells (HUVEC). PPARα and PPARγ significantly reduced interleukin-1β and -6 mRNA expression and their protein levels in the culture medium, and also inhibited cyclooxygenase-2 mRNA expression and their protein levels. Moreover, the mRNA levels of p22phox, a 22-kD subunit and the protein levels of p47phox, a 47-kD subunit of nicotine adenine dinucleotide phosphate (NADPH) oxidase, was decreased by induction of PPARα and PPARγ. This unique anti-inflammatory effect in addition to its hypolipidemic action, may be beneficial in preventung the vascular complications that are induced by hyperlipidemia.

我们检测了过氧化物酶体增殖物激活受体α（PPARα）和PPARγ对培养的人脐静脉内皮细胞（HUVEC）中炎症细胞因子的产生和表达以及对涉及前列腺素和超氧化物产生的酶表达的影响。过氧化物酶体增殖物激活受体α和过氧化物酶体增殖物激活受体γ显著降低细胞培养液中白细胞介素1β和6的mRNA表达及其蛋白水平，同时也抑制环氧化酶2的mRNA表达及其蛋白水平。此外，经PPARα和PPARγ诱导后，烟碱腺嘌呤二核苷酸磷酸（NADPH）氧化酶22 kD亚基p22 phox的mRNA水平和47 kD亚基p47 phox的蛋白水平均降低。这种独特的抗炎作用，除了其降血脂作用，可能是有益的，在preventung血管并发症，由高脂血症诱导。

项目成果

Inoue I, et al.: "The ligands/activators for peroxisome proliferator-activated receptor alpha (PPARalpha) and PPARgamma increase Cu2+, Zn2+-superoxide dismutase and decrease p22phox message expressions in primary endothelial cells."Metabolism. 50(1). 3-11

Inoue I 等人：“过氧化物酶体增殖物激活受体 α (PPARα) 和 PPARgamma 的配体/激活剂可增加原代内皮细胞中 Cu2、Zn2-超氧化物歧化酶并减少 p22phox 信息表达。”代谢。

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Awata T、Inoue K、Kurihara S、Ohkubo T、Inoue I 等人：“(4) 日语中导致 Wolfram 综合征 (WFS1/wolframin) 的基因错义变异：Arg456His 突变对 1 型糖尿病的可能贡献

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