Okamoto Hiroshi, Takasawa Shin
Department of Biochemistry and Advanced Biological Sciences for Regeneration (Kotobiken Medical Laboratories) Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
Nutr Res Rev. 2003 Dec;16(2):253-66. doi: 10.1079/NRR200362.
Poly(ADP-ribose) synthetase/polymerase (PARP) activation causes NAD+ depletion in pancreatic beta-cells, which results in necrotic cell death. On the other hand, ADP-ribosyl cyclase/cyclic ADP-ribose hydrolase (CD38) synthesizes cyclic ADP-ribose from NAD+, which acts as a second messenger, mobilizing intracellular Ca2+ for insulin secretion in response to glucose in beta-cells. PARP also acts as a regenerating gene (Reg) transcription factor to induce beta-cell regeneration. This provides the new concept that NAD+ metabolism can control the cellular function through gene expression. Clinically, PARP could be one of the most important therapeutic targets; PARP inhibitors prevent cell death, maintain the formation of a second messenger, cyclic ADP-ribose, to achieve cell function, and keep PARP functional as a transcription factor for cell regeneration.
聚（ADP - 核糖）合成酶/聚合酶（PARP）的激活会导致胰腺β细胞中的NAD +耗竭，进而导致坏死性细胞死亡。另一方面，ADP - 核糖基环化酶/环ADP - 核糖水解酶（CD38）从NAD +合成环ADP - 核糖，其作为第二信使，在β细胞中响应葡萄糖动员细胞内Ca2 +以促进胰岛素分泌。PARP还作为再生基因（Reg）转录因子诱导β细胞再生。这提供了一个新的概念，即NAD +代谢可以通过基因表达控制细胞功能。临床上，PARP可能是最重要的治疗靶点之一；PARP抑制剂可防止细胞死亡，维持第二信使环ADP - 核糖的形成以实现细胞功能，并使PARP作为细胞再生的转录因子保持功能。
