Reactive oxygen species induced apoptosis in ischemia-reperfusion injury

活性氧诱导缺血再灌注损伤中的细胞凋亡

• 批准号: 11470322
• 负责人: ARAI Toshiyuki
• 金额: $ 9.02万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B).
• 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/en/grant/KAKENHI-PROJECT-11470322/
• 关键词: 6-formylpterin; geranylgeranylacetone; propofol; peroxynitrite; iNOS; thioredoxin; ROS; apoptosis; ラット; 肝細胞; 腫瘍壊死因子; リポポリ多糖類; 活性酸素消去剤; PBN; 活性酸素産生剤; 6FP; 抗Fas抗体; シクロヘキサミド; フローサイトメトリー; カスパーゼ

Effects of 6-formylpterin (6FP), geranylgeranylacetone (GGA) and propofol on the production of reactive oxygen species (ROS) and ischemia-reperfusion injury were investigated using electron paramagnetic resonance (EPR) and flow cytometry.1) Effects of 6FP on the production of nitrotyrosine as a footprint of tyrosine nitration by peroxynitite, a strong oxidant, were examined. The results showed that 6FP was not necessarily a strong scavenger of peroxynitite.2) Effects of 6FP on the production of nitric oxide (NO) in macrophages were examined. The results showed that 6FP suppressed both iNOS induction and NOS activity, which resulted in the inhibition of NO production.3) Effects of GGA on ethanol-induced cytotoxicity in rat hepatocytes were examined. The results showed that GGA facilitated the induction of thioredoxin, an antioxidant, which exerted the cytoprotective effects on the hepatocytes.4) The chemical property of 6FP and its biological functions were examined. The results showed that 6FP reacted with reducing agents, such as NAD(P)H, and generated ROS, which induced apoptosis, suppression of cell proliferation and inhibition of Fas-induced apoptosis.5) Effects of propofol on neuronal damage in focal cerebral ischemia in hyperglycemic rats were examined. The results showed that ppropofol suppressed lactate accumulation and edema formation in brain, which resulted in the attenuation of the neuronal damage.

采用电子顺磁共振（EPR）和流式细胞术研究6-甲酰基蝶呤（6FP）、香叶基香叶丙酮（GGA）和异丙酚对大鼠活性氧（ROS）生成和缺血再灌注损伤的影响。1)考察了6FP作为强氧化剂过氧土硝化酪氨酸的足迹对硝基酪氨酸生成的影响。结果表明，6FP不一定是过氧化物铁矿的强清除剂。2)研究6FP对巨噬细胞一氧化氮（NO）生成的影响。结果表明，6FP抑制了iNOS诱导和NOS活性，从而抑制了NO的产生。3)观察GGA对乙醇诱导的大鼠肝细胞毒性的影响。结果表明，GGA促进了抗氧化剂硫氧还蛋白的产生，对肝细胞具有细胞保护作用。4)研究了6FP的化学性质及其生物学功能。结果表明，6FP与NAD(P)H等还原剂反应生成ROS，诱导细胞凋亡，抑制细胞增殖，抑制fas诱导的细胞凋亡。5)观察异丙酚对高血糖大鼠局灶性脑缺血神经元损伤的影响。结果表明，异丙酚能抑制大鼠脑内乳酸的积累和水肿的形成，从而减轻神经元损伤。

项目成果

Arai T,Endo N, et al.: "6-formylpterin, axanthine oxidase inhibitor, intracellularly generares reactive oxygen species involved in apoptosis and cell proliferation."Free Radic Biol Med. 30. 248-259 (2001)

Arai T、Endo N 等人：“6-甲酰蝶呤，黄嘌呤氧化酶抑制剂，细胞内产生活性氧，参与细胞凋亡和细胞增殖。”Free Radic Biol Med。

Mori H,Arai T, et al: "Effects of 6-formylpterin, a xanthine oxidase inhibitor and a superoxide scavenger on production of nitric oxide in RAW 2647 macrophages."Biochim Biophys Acta. 1474. 93-99 (2000)

Mori H、Arai T 等人：“6-甲酰蝶呤、黄嘌呤氧化酶抑制剂和超氧化物清除剂对 RAW 2647 巨噬细胞中一氧化氮产生的影响。”Biochim Biophys Acta。

Hirota K, Nakamura H, Arai T, Ishii H, Bai J, Itoh T, Fukuda K, Yodoi J: "Geranylgeranylacetone enhances expression of thioredoxin and suppresses ethanol-induced cytotoxicity in cultured hepatocytes."Biochem Biophys Res Commun. 275. 825-830 (2000)

Hirota K、Nakamura H、Arai T、Ishii H、Bai J、Itoh T、Fukuda K、Yodoi J：“香叶基香叶基丙酮增强培养肝细胞中硫氧还蛋白的表达并抑制乙醇诱导的细胞毒性。”Biochem Biophys Res Commun。

Mori H,Arai T, et al.: "Pterin-6-aldehyde,xanthine oxidase inhibitor and superoxide scavenger,directly react with peroxynitrite."Pteridines. 10. 32-34 (1999)

Mori H，Arai T，等人：“蝶呤-6-醛，黄嘌呤氧化酶抑制剂和超氧化物清除剂，直接与过氧亚硝酸盐反应。”蝶啶。

Mori H, Arai T, Ishii H, Endo N, Suzuki T, Fukuda K: "Pterin-6-aldehyde, xanthine oxidase inhibitor and superoxide scavenger, directly react with peroxynitrite."Pteridines. 10. 32-34 (1999)

Mori H、Arai T、Ishii H、Endo N、Suzuki T、Fukuda K：“蝶呤-6-醛、黄嘌呤氧化酶抑制剂和超氧化物清除剂，直接与过氧亚硝酸盐反应。”蝶啶。