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钙离子超载是介导兴奋性神经毒性和多种神经退行性病变的重要细胞机制,胞内能量耗竭是钙超载所致神经细胞死亡的重要原因。脑源胞浆型肌酸激酶(cytosolic creatine kinase,CKBB)能通过催化生成磷酸肌酸来存储能量,提高细胞的荷能状态,对钙超载引发的细胞毒性可能具有调控作用。作者克隆了小鼠CKBB的c DNA,发现过表达CKBB能有效缓解A23187刺激引起的SH-SY5Y细胞内ATP排空,降低能量“感受器”—AMP激活的蛋白激酶(AMP-activated protein kinase,AMPK)—的磷酸化程度,并显著提高细胞存活率。在谷氨酸诱导的原代小脑颗粒神经元的钙超载体系中也证明了CKBB的保护作用。此外,还发现肌酸结合CKBB的双因素保护方案比单独的CKBB干预效果更好,该结果对于肌酸和肌酸激酶的临床应用具有一定的借鉴意义。
Calcium overload is an important cellular mechanism mediating excitotoxicity and various neurodegenerative diseases. Intracellular energy depletion is an important reason for the death of nerve cells caused by calcium overload. Cytoplasmic cytosolic creatine kinase (CKBB) can catalyze the formation of phosphocreatine to store energy, increase the charge state of cells, and may play a regulatory role in cytotoxicity induced by calcium overload. The authors cloned c DNA from mouse CKBB and found that overexpression of CKBB can effectively relieve ATP-evacuation and decrease energy of AMP-activated protein kinase (AMP-activated protein kinase) in SH-SY5Y cells induced by A23187, AMPK) - phosphorylation, and significantly improve cell viability. The protective effect of CKBB was also demonstrated in the calcium overload system of glutamate-induced primary cerebellar granule neurons. In addition, two-factor protection of creatine-binding CKBB was found to be more effective than intervention of CKBB alone, which may be of some reference to the clinical application of creatine and creatine kinase.