CaM-kinasell-dependent commitment to microcystin-induced apoptosis is coupled to cell budding, but not to shrinkage or chromatin hypercondensation
CaM-kinasell-dependent commitment to microcystin-induced apoptosis is coupled to cell budding, but not to shrinkage or chromatin hypercondensation
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DOI：
10.1038/sj.cdd.4401798
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发表时间：
2006-07-01
影响因子：
12.4
通讯作者：
Doskeland, S. O.
中科院分区：
文献类型：
--
作者：
Krakstad, C.;Herfindal, L.;Doskeland, S. O.
蛋白磷酸酶抑制剂微囊藻毒素-LR(MC)通过钙调素依赖的多功能蛋白激酶II(CaMKII)诱导肝细胞凋亡。在MC后的不同时间加入CaMKII拮抗剂，以确定细胞在多长时间内依赖CaMKII活性来执行各种死亡参数。收缩和非极化萌芽是可逆的，与承诺无关。在添加MC(0.5亩M)后15-20分钟观察到一个关键的承诺步骤。此后，CaMKII抑制剂不再防止极化萌发、DNA断裂、蛋白质合成能力丧失和细胞破坏。在加入MC后40分钟发生染色质过度凝聚。总而言之，不可逆转的死亡承诺与极化萌发有关，但与收缩或染色质凝聚无关。当在CaMKII依赖的承诺点之后给予抗氧化剂时，可以阻止染色质缩合，这表明CaMKII介导了活性氧物种性质的第二个信使的积累。
The protein phosphatase inhibitor microcystin-LR (MC) induced hepatocyte apoptosis mediated by the calcium-calmodulin-dependent multifunctional protein kinase II (CaMKII). CaMKII antagonists were added at various times after MC to define for how long the cells depended on CaMKII activity to be committed to execute the various parameters of death. Shrinkage and nonpolarized budding were reversible and not coupled to commitment. A critical commitment step was observed 15-20 min after MC (0.5 mu M) addition. After this, CaMKII inhibitors no longer protected against polarized budding, DNA fragmentation, lost protein synthesis capability, and cell disruption. Commitment to chromatin hypercondensation occurred 40 min after MC addition. In conclusion, irreversible death commitment was coupled to polarized budding, but not to shrinkage or chromatin condensation. Antioxidant prevented chromatin condensation when given after the CaMKII-dependent commitment point, suggesting that CaMKII had mediated the accumulation of a second messenger of reactive oxygen species nature.