ETHANOL ENHANCES ADP-RIBOSYLATION OF PROTEIN IN RAT HEPATOCYTES

被引:8
作者
AKINSHOLA, BE [1 ]
SHARMA, S [1 ]
POTTER, JJ [1 ]
MEZEY, E [1 ]
机构
[1] JOHNS HOPKINS UNIV,SCH MED,DEPT MED,416 HUNTERIAN,725 N WOLFE ST,BALTIMORE,MD 21205
关键词
D O I
10.1002/hep.1840150320
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Decreases in hepatocyte NAD+ produced by ethanol are only partially explained by the increased conversion of NAD+ to NADH and NADP+. The purpose of this study was to determine whether a mechanism for the ethanol-induced decrease in NAD+ is its increased use in ADP-ribosylation. Exposure of hepatocytes in culture for 2 hr to 100 mmol/L ethanol increased the incorporation of C-14-ribose from prelabeled NAD+ into C-14-ribosylated proteins. Poly (ADP-ribose) polymerase activity was increased by exposure of isolated hepatocytes to 100 mmol/L ethanol for 10 min. In hepatocyte culture, increases in poly (ADP-ribose) polymerase were not detected after exposure to 100 mmol/L ethanol for 10 min or 2 hr but rather occurred at 24 hr. Ethanol exposure of hepatocytes in culture for 2 hr, however, decreased the K(m) for NAD+ of poly (ADP-ribose) polymerase. Both nicotinamide and 5-aminobenzamide, which are inhibitors of poly (ADP-ribose) polymerase, prevented the decrease in NAD+ produced by 2-hr exposure of hepatocytes in culture to 100 mmol/L ethanol. The effect of ethanol in decreasing DNA synthesis on days 3 and 4 of culture was not reversed by the inhibitors of poly (ADP-ribose) polymerase. These results indicate that increased ADP-ribosylation of hepatocyte proteins is a mechanism for the effect of ethanol in decreasing NAD+.
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页码:471 / 476
页数:6
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