NITRIC-OXIDE TOXICITY IN ISLET CELLS INVOLVES POLY(ADP-RIBOSE) POLYMERASE ACTIVATION AND CONCOMITANT NAD+ DEPLETION
NITRIC-OXIDE TOXICITY IN ISLET CELLS INVOLVES POLY(ADP-RIBOSE) POLYMERASE ACTIVATION AND CONCOMITANT NAD+ DEPLETION
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DOI：
10.1006/bbrc.1994.1368
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发表时间：
1994-03-30
影响因子：
3.1
通讯作者：
KOLB, H
中科院分区：
文献类型：
--
作者：
RADONS, J;HELLER, B;KOLB, H
先前的研究表明，DNA链断裂是胰岛细胞中一氧化氮毒性的早期结果。我们在这里表明，暴露于化学NO供体的胰岛细胞导致细胞核中ADP-核糖聚合物的形成，伴随着细胞内NAD+的耗竭。ADP-核糖基化抑制剂烟酰胺、3-氨基苯甲酰胺和4-氨基-1，8-萘二甲酰亚胺可在很大程度上阻止胰岛细胞溶解，后者是一种对聚（ADP-核糖基）化具有高选择性的有效新一代化合物。这些发现表明，在胰岛细胞中，聚（ADP-核糖）聚合酶活化在NO毒性中起关键作用。(C)1994年出版社出版。
Previous studies have shown that DNA strand breaks are an early consequence of nitric oxide toxicity in pancreatic islet cells. We show here that exposure of islet cells to chemical NO donors causes the formation of ADP-ribose polymers in cell nuclei, with concomitant depletion of intracellular NAD+. Islet cell lysis was largely prevented by the ADP-ribosylation inhibitors nicotinamide, 3-aminobenzamide, and 4-amino-1,8-naphthalimide, the latter being a potent new-generation compound with high selectivity for poly(ADP-ribosyl)ation. These findings indicate a key role of poly(ADP-ribose) polymerase activation in NO toxicity in islet cells. (C) 1994 Academic Press, Inc.