Nitric oxide induces metallothionein-I gene expression in mesangial cells

In various forms of injury involving the renal glomerulus, mesangial cells are exposed to potentially toxic concentrations of nitric oxide (NO) caused by activation of the inducible isoform of nitric oxide synthase (NOS). Whether mesangial cells possess systems that can defend against NO mediated oxidative injury is unknown. One putative system is Metallothionein (MT). Metallothioneins constitute a family of cysteine proteins and play a significant role as anti-oxidants. The authors assessed whether NO upregulates MT-I expression in cultured glomerular mesangial cells. Northern blot analysis revealed that steady state MT-I mRNA levels were increased by three different NO donors: sodium nitroprusside (SNP), S-nitroso-N-acetyl-DL-penicillamine (SNAP), and Spermine-NONOate (Sper/NO). The increase in MT-I mRNA levels induced by SNAP-derived NO was attenuated by the antioxidant N-acetylcysteine (NAC), a glutathione (GSH) precursor, which indicates that the mechanism of NO-mediated MT-I expression may involve an oxidative stress response. These observations identify MT-I as a putative antioxidant system in NO-mediated mesangial cell injury.