HGF-mediated inhibition of oxidative stress by 8-nitro-cGMP in high glucose-treated rat mesangial cells

作者：Shang Guoguo; Akaike, Takaaki; Jiang Tao; Chen Qi; Zhang Nong; Li Hui^*

来源：Free Radical Research, 2012, 46(10): 1238-1248.

DOI：10.3109/10715762.2012.701292

• hepatocyte growth factor
• oxidative stress
• mesangial cells
• reactive oxygen species
• 8-nitro-cGMP
• Nrf2

Hepatocyte growth factor (HGF) is a potential therapeutic agent for diabetic nephropathy. The mechanisms for the renoprotective eff ect 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) 1-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.

• 出版日期2012-10
• 单位复旦大学