TY - JOUR
T1 - HGF-mediated inhibition of oxidative stress by 8-nitro-cGMP in high glucose-treated rat mesangial cells
AU - Guoguo, Shang
AU - Akaike, Takaaki
AU - Tao, Jiang
AU - Qi, Chen
AU - Nong, Zhang
AU - Hui, Li
N1 - Funding Information:
This was supported for 3 years by grants from the National Natural Science Foundation of China (NSFC 30900538). The authors declared no conflicts of interests. The authors alone are responsible for the content and writing of the paper.
PY - 2012/10
Y1 - 2012/10
N2 - 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.
AB - 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.
KW - 8-nitro-cGMP
KW - Hepatocyte growth factor
KW - Mesangial cells
KW - Nrf2
KW - Oxidative stress
KW - Reactive oxygen species
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U2 - 10.3109/10715762.2012.701292
DO - 10.3109/10715762.2012.701292
M3 - Article
C2 - 22690849
AN - SCOPUS:84866337195
SN - 1071-5762
VL - 46
SP - 1238
EP - 1248
JO - Free Radical Research
JF - Free Radical Research
IS - 10
ER -
