Human alcohol dehydrogenase 1 is an acceptor protein for polyADP-ribosylation.
Human alcohol dehydrogenase 1 is an acceptor protein for polyADP-ribosylation.
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DOI：
10.1016/j.bcp.2019.03.037
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发表时间：
2019-09
影响因子：
5.8
通讯作者：
Miwa, Masanao
中科院分区：
文献类型：
--
作者：
Yamashita, Sachiko;Tanaka, Masakazu;Nodono, Hiroto;Hamada, Akiko;Hamada, Takashi;Hasegawa, Makoto;Nishi, Yoshisuke;Moss, Joel;Miwa, Masanao
乙醇脱氢酶（ADH）对于预防酒精中毒和发育障碍是重要的，并且可能涉及包括神经退行性疾病在内的其他疾病。我们发现，在使用缺乏聚（ADP-核糖）糖水解酶的黑腹果蝇突变体的神经变性模型生物体中，聚ADP-核糖基化的主要受体蛋白是ADH。因此，我们推测，人类ADH活性可能是由聚ADP-核糖基化，翻译后修饰。[32 P]NAD+的放射性在体外通过人聚（ADP-核糖）聚合酶1掺入人ADH 1中，但在使用热灭活的PARP 1或PARP抑制剂3-氨基苯甲酰胺时未掺入。在存在过量ADP-核糖或聚（ADP-核糖）作为竞争物的情况下，掺入的放射性不从ADH 1蛋白中释放。然而，它通过与1 M中性NH 2 OH或0.1 N NaOH孵育而释放，但与0.1 N HCl孵育则不释放，表明ADH 1和聚（ADP-核糖）之间的键是酯键。当在另一种PARP抑制剂奥拉帕尼存在下培养HepG 2细胞（一种人肝癌细胞系）时，细胞的ADH活性显著增加。这些结果表明，聚ADP核糖基化可以调节体内ADH的活性，并可能参与神经退行性变。
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.
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DOI：
10.1016/0925-4439(95)00038-6
发表时间：
1995-05-24
影响因子：
6.2
作者：
MIZUNO, Y;IKEBE, S;OZAWA, T
通讯作者：
OZAWA, T
影响因子：
14.8
作者：
Leidecker O;Bonfiglio JJ;Colby T;Zhang Q;Atanassov I;Zaja R;Palazzo L;Stockum A;Ahel I;Matic I
通讯作者：
Matic I
DOI：
10.1126/science.aat8407
发表时间：
2018-11-02
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kam TI;Mao X;Park H;Chou SC;Karuppagounder SS;Umanah GE;Yun SP;Brahmachari S;Panicker N;Chen R;Andrabi SA;Qi C;Poirier GG;Pletnikova O;Troncoso JC;Bekris LM;Leverenz JB;Pantelyat A;Ko HS;Rosenthal LS;Dawson TM;Dawson VL
通讯作者：
Dawson VL
影响因子：
5.1
作者：
Singh, Mahavir;Kapoor, Aniruddh;Bhatnagar, Aruni
通讯作者：
Bhatnagar, Aruni
影响因子：
14.9
作者：
Altmeyer M;Messner S;Hassa PO;Fey M;Hottiger MO
通讯作者：
Hottiger MO