HGF-mediated inhibition of oxidative stress by 8-nitro-cGMP in high glucose-treated rat mesangial cells
HGF-mediated inhibition of oxidative stress by 8-nitro-cGMP in high glucose-treated rat mesangial cells
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HGF 介导的 8-硝基-cGMP 对高糖处理的大鼠系膜细胞氧化应激的抑制作用
DOI：
10.3109/10715762.2012.701292
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发表时间：
2012-06
影响因子：
3.3
通讯作者：
李慧
中科院分区：
文献类型：
--
作者：
李慧
摘要肝细胞生长因子（HGF）是一种潜在的糖尿病肾病治疗药物。肝细胞生长因子的肾脏保护作用的机制已被广泛研究，但在糖尿病肾病肝细胞生长因子的抗氧化信号很少了解。我们的观察表明，在高糖（HG）处理的大鼠系膜细胞（RMC）中，一种硝化的鸟嘌呤核苷酸，8-硝基鸟苷3′5′-环磷酸（8-nitro-cGMP）减少。而HGF可明显提高细胞内8-nitro-cGMP水平，并显著抑制氧化应激，表现为活性氧和丙二醛水平降低，谷胱甘肽水平升高。可溶性鸟苷酸环化酶（sGC）抑制剂NS-2028和一氧化氮合酶（NOS）抑制剂l-NMMA可阻断HGF引起的8-硝基cGMP水平升高，抑制HGF引起的氧化应激。因此，这两种抑制剂消除了HGF诱导的NF-E2相关因子2（Nrf 2）的核积累和Nrf 2下游谷氨酸-半胱氨酸连接酶催化亚基（GCLC）表达的上调。总之，肝细胞生长因子至少部分地通过增强一氧化氮和随后的8-硝基-cGMP的产生来改善RMC中HG介导的氧化应激。
Abstract Hepatocyte growth factor (HGF) is a potential therapeutic agent for diabetic nephropathy. The mechanisms for the renoprotective effect of HGF have been studied extensively, but antioxidant signalling of HGF in diabetic nephropathy is minimally understood. Our observations indicated that a nitrated guanine nucleotide, 8-nitroguanosine 3′5′-cyclic monophosphate (8-nitro-cGMP) diminished in high glucose (HG)-treated rat mesangial cells (RMC). However, HGF obviously lifted intracellular 8-nitro-cGMP level, which was accompanied by remarkably suppressed oxidative stress as evidenced by decreased reactive oxygen species and malondialdehyde levels and elevated glutathione level. Inhibitor of soluble guanylyl cyclase (sGC) NS-2028 and inhibitor of nitric oxide synthase (NOS) l-NMMA could block increased 8-nitro-cGMP level and repress oxidative stress by HGF. Accordingly, these two inhibitors abrogated HGF-induced nuclear accumulation of NF-E2 related factor 2 (Nrf2) and up-regulation of Nrf2 downstream glutamate-cysteine ligase catalytic subunit (GCLC) expression. In conclusion, HGF ameliorated HG-mediated oxidative stress in RMC at least in part by enhancing nitric oxide and subsequent 8-nitro-cGMP production.
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DOI：
10.1016/j.bbrc.2010.01.119
发表时间：
2010-03-05
影响因子：
3.1
作者：
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DOI：
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发表时间：
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