title: Even after UVA-exposure will nitric oxide protect cells from reactive oxygen intermediate-mediated apoptosis and necrosis.
abstract: Reactive oxygen species (ROS) play a pivotal role in UVA-induced cell damage. As expression of the inducible nitric oxide synthase (iNOS) is a normal response of human skin to UV radiation we examined the role of nitric oxide (NO) as a protective agent during or even after UVA1- or ROS-exposure against apoptosis or necrosis of rat endothelial cells. When added during or up to 2 h subsequent to UVA1 or ROS exposure the NO-donor S-nitroso-cysteine (SNOC) at concentrations from 100-1000 microM significantly protects from both apoptosis as well as necrosis. The NO-mediated protection strongly correlates with complete inhibition of lipid peroxidation (sixfold increase of malonedialdehyde formation in untreated versus 1.2-fold with 1 mM SNOC). NO-mediated protection of membrane function was also shown by the inhibition of cytochrome c leakage in UVA1 treated cells, a process not accompanied by alterations in Bax and Bcl-2 protein levels. Thus, the experiments presented demonstrate that NO exposure during or even after a ROS-mediated toxic insult fully protects from apoptosis or necrosis by maintaining membrane integrity and function.
authors: Research Group Immunobiology, Heinrich-Heine-University Düsseldorf, D-40001 Düsseldorf, Germany.
authors: C V
authors: CV
authors: Suschek
authors: K
authors: K
authors: Briviba
authors: D
authors: D
authors: Bruch-Gerharz
authors: H
authors: H
authors: Sies
authors: K D
authors: KD
authors: Kröncke
authors: V
authors: V
authors: Kolb-Bachofen
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000528:radiation effects*; D002478:Cells, Cultured; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D003574:Cytochrome c Group / Q000378:metabolism; D019610:Cytoprotection / Q000187:drug effects; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000528:radiation effects; D005786:Gene Expression Regulation / Q000528:radiation effects; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects / Q000528:radiation effects; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D009336:Necrosis; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009603:Nitroso Compounds / Q000494:pharmacology; D010100:Oxygen / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012395:Rose Bengal; D026403:S-Nitrosothiols; D026082:Singlet Oxygen; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein
chemical_list: D000975:Antioxidants; C494828:Bax protein, rat; D003574:Cytochrome c Group; D020030:Nitric Oxide Donors; D009603:Nitroso Compounds; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D026403:S-Nitrosothiols; D051028:bcl-2-Associated X Protein; D026082:Singlet Oxygen; D012395:Rose Bengal; D009569:Nitric Oxide; C021315:S-nitrosocysteine; D006861:Hydrogen Peroxide; D003545:Cysteine; D010100:Oxygen