| Autor: |
Tanaka T; Organization of Medical Education, Osaka Medical College, 2-7 Daigakuchou, Takatsuki, Osaka, Japan. t.tanaka.md@gmail.com, Yamamoto D, Sato T, Tanaka S, Usui K, Manabe M, Aoki Y, Iwashima Y, Saito Y, Mino Y, Deguchi H |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of nutritional science and vitaminology [J Nutr Sci Vitaminol (Tokyo)] 2011; Vol. 57 (2), pp. 192-6. |
| DOI: |
10.3177/jnsv.57.192 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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