Kim Hyun-Soo, Chang Woo-Chul, Hwang Ki-Chul, Choi In-Geol, Park Wyun-Kon
Brain Korea 21 Project for Medical Science, Yonsei University, Seoul 120-752, Republic of Korea.
Eur J Pharmacol. 2008 Oct 10;594(1-3):139-45. doi: 10.1016/j.ejphar.2008.07.027. Epub 2008 Jul 17.
Intracellular Ca2+ overload induced by hypoxia-reoxygenation alters Ca2+ homeostasis, which plays an important role in myocardial cell injury. Even though propofol is known as a radical scavenger with Ca2+ channel blocking properties, little is known about cardioprotective effect associated with Ca2+ homeostasis in cardiomyocytes. In the present study, we showed that propofol protects cardiomyocytes against hypoxia-reoxygenation injury. In propofol-treated cardiomyocytes, we observed a decrease in the expression of pro-apoptotic protein Bax, cytochrome c, caspase-3 activation and intracellular Ca2+ content. We also found that propofol treatment enhanced expression of anti-apoptotic protein Bcl-2 and activation of ERK concerned with survival. Propofol attenuated alterations of genes involving Ca2+-regulatory mechanism and significantly modulated abnormal changes of SERCA2a genes in hypoxia-reoxygenated neonatal cardiomyocytes. These results suggest that propofol modulates the expression of genes involved in Ca2+ homeostasis, thereby producing cardioprotective effects through a reduction in apoptotic cell death.
缺氧复氧诱导的细胞内钙离子超载会改变钙离子稳态，这在心肌细胞损伤中起重要作用。尽管丙泊酚是一种具有钙离子通道阻断特性的自由基清除剂，但关于其在心肌细胞中与钙离子稳态相关的心脏保护作用却知之甚少。在本研究中，我们表明丙泊酚可保护心肌细胞免受缺氧复氧损伤。在丙泊酚处理的心肌细胞中，我们观察到促凋亡蛋白Bax、细胞色素c的表达降低，半胱天冬酶-3激活以及细胞内钙离子含量减少。我们还发现丙泊酚处理增强了抗凋亡蛋白Bcl-2的表达以及与存活相关的细胞外信号调节激酶（ERK）的激活。丙泊酚减轻了缺氧复氧新生心肌细胞中涉及钙离子调节机制的基因变化，并显著调节了肌浆网钙ATP酶2a（SERCA2a）基因的异常变化。这些结果表明，丙泊酚调节参与钙离子稳态的基因表达，从而通过减少凋亡性细胞死亡产生心脏保护作用。
