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

Shang Guoguo, Takaaki Akaike, Jiang Tao, Chen Qi, Zhang Nong, Li Hui

Research output: Contribution to journalArticlepeer-review

7 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1238-1248
Number of pages11
JournalFree Radical Research
Volume46
Issue number10
DOIs
Publication statusPublished - 2012 Oct 1

Keywords

  • 8-nitro-cGMP
  • Hepatocyte growth factor
  • Mesangial cells
  • Nrf2
  • Oxidative stress
  • Reactive oxygen species

ASJC Scopus subject areas

  • Biochemistry

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