首页> 外文OA文献 >Induction of endonuclease-mediated apoptosis in tumor cells by C-nitroso-substituted ligands of poly(ADP-ribose) polymerase.
【2h】

Induction of endonuclease-mediated apoptosis in tumor cells by C-nitroso-substituted ligands of poly(ADP-ribose) polymerase.

机译:聚(ADP-核糖)聚合酶的C-亚硝基取代的配体诱导核酸内切酶介导的肿瘤细胞凋亡。

代理获取
本网站仅为用户提供外文OA文献查询和代理获取服务,本网站没有原文。下单后我们将采用程序或人工为您竭诚获取高质量的原文,但由于OA文献来源多样且变更频繁,仍可能出现获取不到、文献不完整或与标题不符等情况,如果获取不到我们将提供退款服务。请知悉。

摘要

6-Nitroso-1,2-benzopyrone and 3-nitrosobenzamide, two C-nitroso compounds that inactivate the eukaryotic nuclear protein poly(ADP-ribose) polymerase [NAD+:poly(adenosine diphosphate D-ribose) ADP-D-ribosyltransferase, ADPRT, EC 2.4.2.30] at one zinc-finger site, completely suppressed the proliferation of leukemic and other malignant human cells and subsequently produced cell death. Tumoricidal concentrations of the drugs were relatively harmless to normal bone marrow progenitor cells and to superoxide formation by neutrophil granulocytes. The cellular mechanism elicited by the C-nitroso compounds consists of apoptosis due to DNA degradation by the nuclear calcium/magnesium-dependent endonuclease. This endonuclease is maintained in a latent form by poly(ADP-ribosyl)ation, but inactivation of ADPRT by C-nitroso drugs derepresses the DNA-degrading activity. ADPRT is thus identified as a critical regulatory enzyme component of a DNA-binding multiprotein system that plays a central function in defining DNA structures in the intact cell.
机译:6-亚硝基1,2,2-苯并吡喃酮和3-亚硝基苯甲酰胺,这两种C-亚硝基化合物,可以使真核细胞核蛋白聚(ADP-核糖)聚合酶失活[NAD +:聚(二磷酸腺苷D-核糖)ADP-D-核糖基转移酶,ADPRT ,EC 2.4.2.30]在一个锌指位点完全抑制了白血病和其他恶性人类细胞的增殖,并随后导致了细胞死亡。药物的杀肿瘤浓度对正常的骨髓祖细胞和嗜中性粒细胞的超氧化物形成相对无害。 C-亚硝基化合物引发的细胞机制包括由于核钙/镁依赖性核酸内切酶使DNA降解而引起的细胞凋亡。该核酸内切酶通过聚(ADP-核糖基)化作用保持潜在形式,但是C-亚硝基药物使ADPRT失活会降低DNA降解活性。因此,ADPRT被认为是DNA结合多蛋白系统的关键调节酶成分,在完整细胞的DNA结构定义中起着核心作用。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
代理获取

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号