NDLI: S-nitrosylation of tissue-type plasminogen activator confers vasodilatory and antiplatelet properties on the enzyme.

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S-nitrosylation of tissue-type plasminogen activator confers vasodilatory and antiplatelet properties on the enzyme.

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S-nitrosylation of tissue-type plasminogen activator confers vasodilatory and antiplatelet properties on the enzyme.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Singel, D. Loscalzo, J. Simon, D. I. Francis, S. Stamler, J. S. Jaraki, O. Osborne, J. A. Mullins, M.
Description	Author Affiliation: Stamler JS ( Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, MA.);
Abstract	Tissue-type plasminogen activator (t-PA) reacts upon exposure to endothelium-derived relaxing factor (EDRF) by way of the enzyme's single free sulfhydryl (Cys-83) to form a stable S-nitrosothiol protein adduct. S-nitrosylation endows t-PA with potent vasodilatory and antiplatelet properties that are accompanied by elevations in intracellular cyclic GMP analogous to those induced by low molecular weight (e.g., S-nitroso amino acid) S-nitrosothiols. Moreover, this chemical modification does not adversely affect the catalytic efficiency of t-PA, the fibrin stimulation of this activity, the binding of t-PA to fibrinogen, or the interaction of the enzyme with its physiologic serine protease inhibitor, plasminogen-activator inhibitor type I. The coupling of vasodilatory, antiplatelet, and fibrinolytic properties in one molecule makes the S-nitrosylated t-PA a unique molecular species and may provide insight into the mechanisms by which the endothelium maintains vessel patency. These data also suggest a pharmacologic approach to treatment of thromboocclusive disorders.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	17
Volume Number	89
Language	English
Publisher	National Academy of Sciences
Publisher Date	1992-10-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Nitroso Compounds Chemistry Tissue Plasminogen Activator Vasodilator Agents Animals Cells, Cultured Cyclic GMP Metabolism Fibrin Fibrinogen In Vitro Techniques Kinetics Pharmacology Platelet Aggregation Drug Effects Platelet Aggregation Inhibitors Structure-Activity Relationship Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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