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Adenosine thiamine triphosphate (AThTP) inhibits poly(ADP-ribose) polymerase-1 (PARP-1) activity.
- Source :
-
Journal of nutritional science and vitaminology [J Nutr Sci Vitaminol (Tokyo)] 2011; Vol. 57 (2), pp. 192-6. - Publication Year :
- 2011
-
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.
- Subjects :
- Adenosine Triphosphate chemical synthesis
Adenosine Triphosphate chemistry
Animals
Binding Sites
Diabetes Complications drug therapy
Diabetes Complications metabolism
Enzyme Inhibitors chemistry
Humans
Models, Biological
Molecular Structure
NAD chemistry
Recombinant Proteins
Thiamine therapeutic use
Thiamine Triphosphate chemical synthesis
Thiamine Triphosphate chemistry
Adenosine Triphosphate pharmacology
Enzyme Inhibitors pharmacology
NAD deficiency
Poly(ADP-ribose) Polymerase Inhibitors
Thiamine Triphosphate pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1881-7742
- Volume :
- 57
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Journal of nutritional science and vitaminology
- Publication Type :
- Academic Journal
- Accession number :
- 21697640
- Full Text :
- https://doi.org/10.3177/jnsv.57.192