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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antioxidants / pharmacology
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Apoptosis / radiation effects*
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Cells, Cultured
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Cysteine / analogs & derivatives
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Cysteine / pharmacology
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Cytochrome c Group / metabolism
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Cytoprotection / drug effects
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Endothelium, Vascular / cytology
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Endothelium, Vascular / drug effects
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Endothelium, Vascular / radiation effects
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Gene Expression Regulation / radiation effects
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Hydrogen Peroxide / metabolism
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Hydrogen Peroxide / pharmacology
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Lipid Peroxidation / drug effects
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Lipid Peroxidation / radiation effects
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Microscopy, Fluorescence
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Mitochondria / drug effects
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Mitochondria / metabolism
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Mitochondria / radiation effects
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Necrosis
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Nitric Oxide / metabolism*
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Nitric Oxide / pharmacology
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Nitric Oxide Donors / pharmacology
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Nitroso Compounds / pharmacology
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Oxygen / metabolism
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Rats
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Rats, Wistar
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Reactive Oxygen Species / metabolism*
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Rose Bengal
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S-Nitrosothiols*
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Singlet Oxygen
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Ultraviolet Rays*
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bcl-2-Associated X Protein
Substances
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Antioxidants
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Bax protein, rat
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Cytochrome c Group
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Nitric Oxide Donors
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Nitroso Compounds
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Reactive Oxygen Species
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S-Nitrosothiols
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bcl-2-Associated X Protein
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Singlet Oxygen
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Rose Bengal
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Nitric Oxide
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S-nitrosocysteine
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Hydrogen Peroxide
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Cysteine
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Oxygen