Journal of Nutritional Science and Vitaminology
Online ISSN : 1881-7742
Print ISSN : 0301-4800
ISSN-L : 0301-4800
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Adenosine Thiamine Triphosphate (AThTP) Inhibits Poly(ADP-Ribose) Polymerase-1 (PARP-1) Activity
Takao TANAKADaisuke YAMAMOTOTakaji SATOSunao TANAKAKazuya USUIMiki MANABEYui AOKIYasuki IWASHIMAYoshihiro SAITOYoshiki MINOHirofumi DEGUCHI
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2011 Volume 57 Issue 2 Pages 192-196

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Abstract

Overactivation of poly(ADP-ribose) polymerase-1 (PARP-1) has been demonstrated to result in various stress-related diseases, including diabetes mellitus. Deficiency of cellular nicotinamide adenine dinucleotide (NAD+) content, consumed by PARP-1 to add ADP-ribose moieties onto target proteins, contributes to pathophysiological conditions. Adenosine thiamine triphosphate (AThTP) exists in small amounts in mammals; however, the function(s) of this metabolite remains unresolved. The structure of AThTP resembles NAD+. Recent experimental studies demonstrate beneficial impacts of high-dose thiamine treatment of diabetic complications. These findings have led us to hypothesize that AThTP may modulate the activity of PARP-1. We have chemically synthesized AThTP and evaluated the effect of AThTP on recombinant PARP-1 enzyme activity. AThTP inhibited the PARP-1 activity at 10 μM, and a structural model of the PARP-1-AThTP complex highlighted the AThTP binding site. The results provide new insights into the pharmacological importance of AThTP as an inhibitor of PARP-1.

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© 2011 by the Center for Academic Publications Japan
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