SOD1 suppresses maternal hyperglycemia-increased iNOS expression and consequent nitrosative stress in diabetic embryopathy.
SOD1 suppresses maternal hyperglycemia-increased iNOS expression and consequent nitrosative stress in diabetic embryopathy.
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DOI：
10.1016/j.ajog.2012.02.011
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发表时间：
2012-05
影响因子：
9.8
通讯作者：
Yang P
中科院分区：
文献类型：
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作者：
Weng H;Li X;Reece EA;Yang P
高血压诱导氧化应激并增加诱导型一氧化氮合酶（iNOS）的表达。我们假设氧化应激是负责高血糖诱导的iNOS表达。在暴露于5 mM葡萄糖或高葡萄糖（25 mM）的PYS-2细胞中，在有或没有SOD 1（铜锌超氧化物歧化酶1）处理的情况下，测定iNOS-荧光素酶活性、亚硝基化蛋白、脂质过氧化标记物4-HNE和MDA。在野生型胚胎和来自非糖尿病和糖尿病母鼠的SOD 1过表达胚胎中评估iNOS蛋白和mRNA、亚硝基化蛋白和裂解的caspase-3和-8的水平。SOD 1处理减少了高糖诱导的氧化应激，如4-HNE和MDA减少所证明的，并且它阻断了高糖增加的iNOS表达、iNOS荧光素酶活性和亚硝基化蛋白。体内SOD 1过表达抑制高血糖增加的iNOS表达和亚硝基化蛋白，并阻断caspase-3和-8裂解。我们的结论是，氧化应激诱导iNOS的表达，亚硝化应激和细胞凋亡在糖尿病胚胎病。
Hyperglycemia induces oxidative stress and increases inducible nitric oxide synthase (iNOS) expression. We hypothesized that oxidative stress is responsible for hyperglycemia-induced iNOS expression. iNOS-luciferase activities, nitrosylated protein, lipidperoxidation markers 4-HNE and MDA were determined in PYS-2 cells exposed to 5 mM glucose or high glucose (25 mM) with or without SOD1 (copper zinc superoxide dismutase 1) treatment. Levels of iNOS protein and mRNA, nitrosylated protein, and cleaved caspase-3 and -8 were assessed in wild-type embryos and SOD1 overexpressing embryos from non-diabetic and diabetic dams. SOD1 treatment diminished high glucose-induced oxidative stress, as evidenced by 4-HNE and MDA reductions, and it blocked high glucose-increased iNOS expression, iNOS-luciferase activities, and nitrosylated protein. in vivo SOD1 overexpression suppressed hyperglycemia-increased iNOS expression and nitrosylated protein, and it blocked caspase-3 and -8 cleavage. We conclude that oxidative stress induces iNOS expression, nitrosative stress, and apoptosis in diabetic embryopathy.