Ishii Masakazu, Shimizu Shunichi, Hagiwara Tamio, Wajima Teruaki, Miyazaki Akira, Mori Yasuo, Kiuchi Yuji
Department of Pathophysiology, School of Pharmaceutical Sciences, Showa University, Tokyo, Japan.
J Pharmacol Sci. 2006 Jun;101(2):174-8. doi: 10.1254/jphs.scj06001x. Epub 2006 Jun 10.
Intracellular ADP-ribose is an activator of TRPM2, which is a Ca2+-permeable channel and mediates H2O2-induced cell death, in the TRPM2-expressing rat beta-cell line RIN-5F. We examined the effect of extracellular-added ADP-ribose on intracellular Ca2+ concentration in RIN-5F cells. ADP-ribose induced Ca2+ release from the thapsigargin-sensitive Ca2+ store, but not Ca2+ entry across the plasma membrane. A phospholipase C (PLC) inhibitor and a non-specific IP3 receptor inhibitor blocked its Ca2+ release. H2O2-induced Ca2+ entry through TRPM2 was not affected by extracellular ADP-ribose. These findings suggest that extracellular-added ADP-ribose induces Ca2+ release through the PLC-IP3 pathway and does not act as a TRPM2 activator.
在表达瞬时受体电位阳离子通道蛋白2（TRPM2）的大鼠β细胞系RIN-5F中，细胞内ADP-核糖是TRPM2的激活剂，TRPM2是一种Ca2+可渗透通道，介导H2O2诱导的细胞死亡。我们研究了细胞外添加的ADP-核糖对RIN-5F细胞内Ca2+浓度的影响。ADP-核糖诱导了从毒胡萝卜素敏感的Ca2+储存库释放Ca2+，但未诱导Ca2+跨质膜内流。磷脂酶C（PLC）抑制剂和非特异性肌醇三磷酸（IP3）受体抑制剂阻断了其Ca2+释放。H2O2诱导的通过TRPM2的Ca2+内流不受细胞外ADP-核糖的影响。这些发现表明，细胞外添加的ADP-核糖通过PLC-IP3途径诱导Ca2+释放，并且不作为TRPM2激活剂起作用。
