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Cytoprotective Effects of Nicotinamide Derivatives in Endothelial Cells
Authors:E M Slominska  A Yuen  L Osman  J Gebicki  M H Yacoub  R T Smolenski
Institution:1. Department of Biochemistry , Medical University of Gdansk , Poland;2. Heart Science Centre , Imperial College London , Harefield, United Kingdom;3. Department of Applied Radiation Chemistry , Technical University of Lodz , Poland;4. Department of Biochemistry , Medical University of Gdansk , Poland;5. Heart Science Centre , Imperial College London , Harefield, United Kingdom
Abstract:Following discovery of NAD+-dependent reactions that control gene expression, cytoprotection, and longevity, there has been a renewed therapeutic interest in precursors, such as nicotinamide and its derivatives. We tested 20 analogues of nicotinamide for their ability to protect endothelial cells from peroxynitrite stress and their effect on poly (ADP-ribose) polymerase (PARP) activity. Several nicotinamide derivatives protected endothelial cells from peroxynitrite-induced depletion of cellular NAD+ and ATP concentrations, but only some of these compounds inhibited PARP. We conclude that some nicotinamide derivatives provide protection of endothelial cells against peroxynitrite-induced injury independent of inhibition of PARP activity. Preservation of the NAD+ pool was a common effect of these compounds.
Keywords:Nicotinamide  endothelium  cytoprotection  poly(ADP-ribose) polymerase (PARP)  NAD  ATP
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