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Human alcohol dehydrogenase 1 is an acceptor protein for polyADP-ribosylation
- Source :
- Biochem Pharmacol
- Publication Year :
- 2019
- Publisher :
- Elsevier BV, 2019.
-
Abstract
- Alcohol dehydrogenase (ADH) is important for preventing alcohol toxicity and developmental disorders, and may be involved in other diseases including neurodegenerative diseases. We found that the major acceptor protein of polyADP-ribosylation in a model organism of neurodegeneration using a Drosophila melanogaster mutant lacking poly(ADP-ribose) glycohydrolase, was ADH. Thus we postulated that human ADH activity might be regulated by polyADP-ribosylation, a post-translational modification. The radioactivity of [32P]NAD+ was incorporated into human ADH1 by human poly(ADP-ribose) polymerase 1 in vitro, but was not incorporated when heat-inactivated PARP1 or a PARP inhibitor, 3-aminobenzamide, was used. The incorporated radioactivity was not released from ADH1 protein in the presence of excess amount of ADP-ribose or poly(ADP-ribose) as competitors. However, it was released by incubation with 1 M neutral NH2OH or 0.1 N NaOH, but was not with 0.1 N HCl, suggesting the bond between ADH1 and poly(ADP-ribose) is an ester linkage. When HepG2 cells, a human hepatoma cell line, were cultured in the presence of another PARP inhibitor, olaparib, ADH activity of the cell was significantly increased. These results suggest that polyADP-ribosylation could regulate ADH activity in vivo and might be involved in neurodegeneration.
- Subjects :
- 0301 basic medicine
Cell Survival
Mutant
Poly (ADP-Ribose) Polymerase-1
Poly(ADP-ribose) Polymerase Inhibitors
Biochemistry
Piperazines
Article
Olaparib
03 medical and health sciences
chemistry.chemical_compound
0302 clinical medicine
PARP1
medicine
Animals
Humans
Alcohol dehydrogenase
Pharmacology
biology
Neurodegeneration
Alcohol Dehydrogenase
Hep G2 Cells
medicine.disease
In vitro
Drosophila melanogaster
030104 developmental biology
chemistry
030220 oncology & carcinogenesis
PARP inhibitor
biology.protein
Phthalazines
NAD+ kinase
Subjects
Details
- ISSN :
- 00062952
- Volume :
- 167
- Database :
- OpenAIRE
- Journal :
- Biochemical Pharmacology
- Accession number :
- edsair.doi.dedup.....17b3108ea64272cf676281b3bf4cce6e