首页    期刊浏览 2024年12月01日 星期日
登录注册

文章基本信息

  • 标题:Adenosine Thiamine Triphosphate (AThTP) Inhibits Poly(ADP-Ribose) Polymerase-1 (PARP-1) Activity
  • 本地全文:下载
  • 作者:Takao TANAKA ; Daisuke YAMAMOTO ; Takaji SATO
  • 期刊名称:Journal of Nutritional Science and Vitaminology
  • 印刷版ISSN:0301-4800
  • 电子版ISSN:1881-7742
  • 出版年度:2011
  • 卷号:57
  • 期号:2
  • 页码:192-196
  • DOI:10.3177/jnsv.57.192
  • 出版社:Center for Academic Publications Japan
  • 摘要: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 μ M , 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.
  • 关键词:adenosine thiamine triphosphate;poly(ADP-ribose) polymerase-1
国家哲学社会科学文献中心版权所有