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.
Datta
Prasun K
PK
Department of Neuroscience, Center for Neurovirology, Temple University School of Medicine, Philadelphia, PA 19122, USA. dattapk@temple.edu
Lianos
Elias A
EA
D000818:Animals; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D019084:Fluorescent Antibody Technique, Indirect; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008668:Metallothionein / Q000096:biosynthesis / Q000235:genetics*; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics*
D020030:Nitric Oxide Donors; D012333:RNA, Messenger; D009599:Nitroprusside; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D008668:Metallothionein