Chan S O, Runko E, Anyane-Yeboa K, Ko L, Chiu F C
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Neurochem Res. 1998 Mar;23(3):393-400. doi: 10.1023/a:1022417819356.
Extensive necrotic death of MSN neuroblastoma cells could be induced after incubation with the calcium ionophore, A23187. The reaction was concentration-dependent and time course-dependent. Levels of the 66 kd/alpha-internexin neurofilament protein (NF-66) and the cognate heat shock protein 70 (Hsc 70) decreased during the Ca2+-activated cell death. Addition of the calcium chelator, ethylene glycol-bis(beta-aminoethyl ether) N,N,N',N'-tetraacetic acid (EGTA) restored the normal level of NF-66 and partially that of the Hsc 70. Use of either calpain I or calpain II inhibitor could alleviate the reduction of 66 kd protein during the ionophore treatment whereas only calpain I inhibitor treatment was effective in restoring the normal level of the Hsc 70. Neither of these calpain inhibitors could block the ionophore triggered cell death. EGTA was toxic to cells in a wide range of concentration suggesting a calcium-independent activation of cell death mechanism.
在与钙离子载体A23187孵育后，可诱导MSN神经母细胞瘤细胞发生广泛的坏死性死亡。该反应呈浓度依赖性和时间进程依赖性。在钙离子激活的细胞死亡过程中，66 kd/α-中间丝蛋白（NF-66）和同源热休克蛋白70（Hsc 70）的水平降低。添加钙螯合剂乙二醇双（β-氨基乙基醚）N,N,N',N'-四乙酸（EGTA）可恢复NF-66的正常水平，并部分恢复Hsc 70的正常水平。使用钙蛋白酶I或钙蛋白酶II抑制剂均可减轻离子载体处理过程中66 kd蛋白的减少，而只有钙蛋白酶I抑制剂处理可有效恢复Hsc 70的正常水平。这些钙蛋白酶抑制剂均不能阻断离子载体触发的细胞死亡。EGTA在广泛的浓度范围内对细胞有毒性，提示细胞死亡机制存在不依赖钙的激活。
