Ca^(2+)/CaMKⅡ信号通路在肿瘤坏死因子-α诱导心肌肥大中的作用  

Ca^(2+)/calmodulin-dependent kinaseⅡare involved in tumor necrosis factor α-induced cardiomyocyte hypertrophy in rats

作　　者：王桂君[1] 姚玉胜[2] 王洪新[3] 

机构地区：[1]辽宁医学院附属第一医院 [2]辽宁医学院附属第二医院 [3]辽宁医学院药理学教研室,辽宁锦州121000

出　　处：《中国药理学通报》2010年第3期387-391,共5页Chinese Pharmacological Bulletin

摘　　要：目的研究钙调素依赖蛋白激酶Ⅱ(CaMKⅡ)信号通路在肿瘤坏死因子-α(TNF-α)诱导心肌细胞肥大中的作用。方法Lowry法测心肌细胞蛋白含量;计算机图像分析系统测心肌细胞体积;[3H]-亮氨酸参入法测心肌细胞蛋白合成;Till阳离子测定系统观察胞内[Ca2+]i瞬变;Westernblot法测定CaMKⅡδB的表达。结果①TNF-α(100μg.L-1)明显诱导心肌细胞蛋白含量、蛋白合成及体积的增加,CaMKⅡ特异性抑制剂KN93(0.2μmol.L-1)明显抑制TNF-α诱导的心肌肥大,但对正常心肌细胞生长无影响。②TNF-α引起心肌细胞内钙离子浓度([Ca2+]i)瞬间变化幅度增高,KN93明显降低TNF-α诱导的上述改变。③TNF-α明显增强心肌细胞内CaMKⅡδB的表达。结论TNF-α可能通过引起心肌细胞[Ca2+]i升高,促进CaMKⅡδB表达诱导心肌细胞肥大的。Aim To investigate whether Ca2＋/calmodulin-dependent kinase Ⅱ（CaMKⅡ）contribute to tumor necrosis factor α（TNF-α）-induced cardiomyocyte hypertrophy.Methods The protein content was assayed with Lowry＇s method.The cardiomyocytes volumes were measured by computer photograph analysis system.The protein synthesis was assayed with[3H]-lencine incorporation method.[Ca2＋]i transient was measured by Till image system by cell-loading Fura-2/AM.The expression of CaMKⅡδB was determined by Western blot.Results ① TNF-α significantly induced the increase of protein content,[3H]-leucine incorporation and cell size;These responses were significantly suppressed by KN93,a selective CaMKⅡ inhibitor.② TNF-α increased the amplitude of the spontaneous Ca2＋ transients in cultured ventricular myocytes from the neonatal rat;CaMKⅡ inhibitor KN93 can suppress the elevation induced by TNF-α.③ TNF-α significantly increased the expression of CaMKⅡδB.Concluslon CaMKⅡ signal pathway are involved in TNF-α-induced cardiomyocyte hypertrophy in rats.

关 键 词：心肌肥厚 肿瘤坏死因子-Α 钙离子 钙调素依赖蛋白激酶 信号转导 KN93 

分 类 号：R332[医药卫生—人体生理学] R322.11[医药卫生—基础医学]