Shao H, Zhou J, Ewald S J
Department of Pathobiology, Auburn University, Alabama 36849-5519, USA.
Cell Immunol. 1995 Aug;164(1):11-9. doi: 10.1006/cimm.1995.1137.
We demonstrated previously that ethanol enhances apoptosis of murine thymocytes. In this report, we determined intracellular cAMP and cytosolic free calcium ([Ca2+]i) levels in mouse thymocytes following acute exposure to ethanol and investigated the involvement of cAMP, [Ca2+]i, protein kinase A (PKA), and protein kinase C (PKC) in thymocyte apoptotic death induced by ethanol. It was found that ethanol did not alter basal cAMP levels, but produced a dose-dependent, prolonged small [Ca2+]i increase within thymocytes. This dose dependence of [Ca2+]i increase was paralleled by the magnitude of DNA fragmentation induced by ethanol at various concentrations. Additionally, the ethanol-enhanced DNA fragmentation was blocked by H7, a PKC inhibitor, but not by potent PKA inhibitors having little or no effect on PKC. These data suggest that both [Ca2+]i increase and PKC activation triggered by ethanol may belong to the signal pathway(s) leading to thymocyte programmed death.
我们先前已证明乙醇可增强小鼠胸腺细胞的凋亡。在本报告中，我们测定了急性暴露于乙醇后小鼠胸腺细胞内的环磷酸腺苷（cAMP）和胞质游离钙（[Ca2+]i）水平，并研究了cAMP、[Ca2+]i、蛋白激酶A（PKA）和蛋白激酶C（PKC）在乙醇诱导的胸腺细胞凋亡死亡中的作用。结果发现，乙醇并未改变基础cAMP水平，但在胸腺细胞内产生了剂量依赖性、持续时间较长的小幅度[Ca2+]i升高。这种[Ca2+]i升高的剂量依赖性与不同浓度乙醇诱导的DNA片段化程度平行。此外，乙醇增强的DNA片段化被PKC抑制剂H7阻断，但不受对PKC几乎没有影响的强效PKA抑制剂的阻断。这些数据表明，乙醇引发的[Ca2+]i升高和PKC激活可能都属于导致胸腺细胞程序性死亡的信号通路。
