Adenosine Thiamine Triphosphate (AThTP) Inhibits Poly(ADP-Ribose) Polymerase-1 (PARP-1) Activity

• TANAKA Takao

  Organization of Medical Education, Osaka Medical College

• YAMAMOTO Daisuke

  Biomedical Computation Center, Osaka Medical College

• SATO Takaji

  Laboratory of Analytical Chemistry, Osaka University of Pharmaceutical Sciences

• TANAKA Sunao

  Human Health Sciences, Graduate School of Medicine Kyoto University

• USUI Kazuya

  Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences

• MANABE Miki

  Laboratory of Pharmacotherapy, Osaka University of Pharmaceutical Sciences

• AOKI Yui

  Laboratory of Analytical Chemistry, Osaka University of Pharmaceutical Sciences

• IWASHIMA Yasuki

  Laboratory of Analytical Chemistry, Osaka University of Pharmaceutical Sciences

• SAITO Yoshihiro

  Laboratory of Analytical Chemistry, Osaka University of Pharmaceutical Sciences

• MINO Yoshiki

  Laboratory of Analytical Chemistry, Osaka University of Pharmaceutical Sciences

• DEGUCHI Hirofumi

  Organization of Medical Education, Osaka Medical College

抄録

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.

収録刊行物

• Ｊｏｕｒｎａｌ　ｏｆ　Ｎｕｔｒｉｔｉｏｎａｌ　Ｓｃｉｅｎｃｅ　ａｎｄ　Ｖｉｔａｍｉｎｏｌｏｇｙ

  Ｊｏｕｒｎａｌ　ｏｆ　Ｎｕｔｒｉｔｉｏｎａｌ　Ｓｃｉｅｎｃｅ　ａｎｄ　Ｖｉｔａｍｉｎｏｌｏｇｙ 57 (2), 192-196, 2011

  一般財団法人 学会誌刊行センター

キーワード

• adenosine thiamine triphosphate
• poly(ADP-ribose) polymerase-1

詳細情報

• CRID: 1390001206326692224
• NII論文ID: 10030029043
• NII書誌ID: AA00703822
• DOI: 10.3177/jnsv.57.192
• COI: 1:CAS:528:DC%2BC3MXlvVensro%3D
• ISSN: 18817742
• ISSN: 03014800
• NDL書誌ID: 11054201
• Web Site: https://ndlsearch.ndl.go.jp/books/R000000004-I11054201
• Web Site: https://search.jamas.or.jp/link/ui/2012060952
• 本文言語コード: en
• データソース種別:
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