Ferritin may mediate SIN-1-induced protection against oxidative stress.
In porcine aortic endothelial cells, a 20-h incubation with hydrogen peroxide (0.5 mM) markedly reduced the number of viable cells. A 6-h preincubation with linsidomine (SIN-1, 0.5 mM) protected endothelial cells from hydrogen peroxide-dependent cytotoxicity and increased the surviving endothelial cell fraction by 85%. This protection was associated with a 2.5-fold induction of ferritin heavy chain mRNA and ferritin protein by SIN-1. The nitric oxide donor glyceryl trinitrate was also found to induce transcriptional and translational expression of ferritin heavy chain. A protective effect comparable to SIN-1 was observed when preincubating the cells with iron-free apoferritin (1 mg/ml). These findings suggest that ferritin induction, presumably via release of nitric oxide, may be a mechanism underlying long-term cytoprotection by SIN-1 against oxidative stress.
Oberle
S
S
Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle (Saale), Germany.
Schröder
H
H
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005293:Ferritins / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008981:Molsidomine / Q000031:analogs & derivatives* / Q000494:pharmacology; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics; D013552:Swine
D000975:Antioxidants; D012333:RNA, Messenger; C002385:linsidomine; D005293:Ferritins; D006861:Hydrogen Peroxide; D008981:Molsidomine