Reduced stress defense in heme oxygenase 1-deficient cells
Reduced stress defense in heme oxygenase 1-deficient cells
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DOI：
10.1073/pnas.94.20.10925
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发表时间：
1997-09-30
影响因子：
11.1
通讯作者：
Tonegawa, S
中科院分区：
文献类型：
--
作者：
Poss, KD;Tonegawa, S
胁迫的哺乳动物细胞上调血红素加氧酶1（HMOX1; EC 1.14.99.3），该酶1.14.99.3），将血红素分解为双脂蛋白，一氧化碳和游离铁。为了评估HMOX1在细胞抗氧化剂防御中的潜在作用，我们分析了缺乏功能性HMOX1对氧化挑战的小鼠的细胞反应。当暴露于HEMIN，过氧化氢，帕拉酸酯或氯化镉时，培养的HMOX1（ - / - ）胚胎成纤维细胞表现出很高的氧自由基产生，并且它们对由HEMIN和过氧化氢的细胞毒性过敏。此外，年轻的成年HMOX1（ - / - ）小鼠容易受到死亡率和肝坏死的攻击，当受到内毒素挑战时，我们的体外和IRT体内结果提供了遗传证据，即HMOX1上调HMOX1可作为一种适应性机制，可作为一种适应性机制，可保护细胞免受氧化损害的损害损害的损害。在压力期间。
Stressed mammalian cells up-regulate heme oxygenase 1 (Hmox1; EC 1.14.99.3), which catabolizes heme to biliverdin, carbon monoxide, and free iron. To assess the potential role of Hmox1 in cellular antioxidant defense, we analyzed the responses of cells from mice lacking functional Hmox1 to oxidative challenges. Cultured Hmox1(-/-) embryonic fibroblasts demonstrated high oxygen free radical production when exposed to hemin, hydrogen peroxide, paraquat, or cadmium chloride, and they were hypersensitive to cytotoxicity caused by hemin and hydrogen peroxide. Furthermore, young adult Hmox1(-/-) mice were vulnerable to mortality and hepatic necrosis when challenged with endotoxin, Our in vitro and irt vivo results provide genetic evidence that up-regulation of Hmox1 serves as an adaptive mechanism to protect cells from oxidative damage during stress.