Nitric oxide protects endothelial cells from tumor necrosis factor-alpha-mediated cytotoxicity: possible involvement of cyclic GMP.
In cultured endothelial cells, incubation with TNF-alpha (50 ng/ml) for 48 h markedly reduced viability of endothelial cells. A 6 h preincubation with Sper/NO (0.03--1 microM) protected endothelial cells in a concentration-dependent manner and increased viability by 63% of control. The NO scavenger PTIO (30 microM) completely abolished cytoprotection by Sper/NO. A cytoprotective effect comparable to Sper/NO was observed when preincubating the cells with 8-bromo cyclic GMP (1-10 microM). Moreover, no protection by Sper/NO occurred in the presence of ODQ (0.1 microM), a selective inhibitor of soluble guanylyl cyclase. Our results demonstrate that NO produces a long-term endothelial protection against cellular injury by TNF-alpha, presumably via a cyclic GMP-dependent pathway.
Polte
T
T
Department of Pharmacology and Toxicology, School of Pharmacy, Martin Luther University, Halle (Saale), Germany.
Oberle
S
S
Schröder
H
H
D000818:Animals; D002417:Cattle; D002460:Cell Line; D006152:Cyclic GMP / Q000276:immunology / Q000502:physiology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology; D009569:Nitric Oxide / Q000502:physiology*; D011651:Pulmonary Artery / Q000166:cytology; D013096:Spermine / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000502:physiology*
D014409:Tumor Necrosis Factor-alpha; D013096:Spermine; D009569:Nitric Oxide; D006152:Cyclic GMP