Hammerschmidt S, Bell M, Büchler N, Wahn H, Remkes H, Lohse M J, Neubauer S
Department of Medicine Pharmacology, University of Würzburg, Würzburg, Germany.
Biochim Biophys Acta. 2000 Nov 15;1502(3):471-80. doi: 10.1016/s0925-4439(00)00070-3.
Creatine kinase (CK) plays a crucial role in myocardial energy metabolism. Alterations in CK gene expression are found in hypertrophied and failing heart, but the mechanisms behind these changes are unclear. This study tests the hypothesis that increased adrenergic stimulation, which is observed in heart failure, induces changes of myocardial CK-activity, -isoenzyme distribution and -gene expression that are characteristic of the failing and hypertrophied heart. Isolated rat hearts were perfused (constant pressure of 80 mmHg) with red cell suspensions. Following a 20-min warm-up period, perfusion for 3 h with 10(-8) M (iso 3 h) or without (control 3 h) isoproterenol was started or experiments were immediately terminated (control 0 h). Left ventricular tissue was analyzed for total CK-activity, CK-isoenzyme distribution and, by use of quantitative RT-PCR, for B-CK, M-CK, mito-CK and GAPDH- (as internal standard) mRNA. After beta-adrenergic stimulation (iso 3 h) but not after control perfusion (control 3 h) a roughly threefold increase in B-CK mRNA levels and a decrease in M-CK mRNA levels by 18% was found. There were no significant differences among the three groups in total CK-activity and in distribution of CK-MM, CK-BB, CK-MB and mito-CK. Thus, beta-adrenergic stimulation induces a switch in CK gene expression from M-CK to B-CK, which is characteristic for the hypertrophied and failing heart. This may be interpreted as an adaptive mechanism making energy transduction via CK more efficient at times of increased metabolic demand.
肌酸激酶（CK）在心肌能量代谢中起着至关重要的作用。在肥厚和衰竭的心脏中发现了CK基因表达的改变，但其背后的机制尚不清楚。本研究检验了这样一个假设，即在心力衰竭中观察到的肾上腺素能刺激增加，会诱导心肌CK活性、同工酶分布和基因表达的变化，这些变化是衰竭和肥厚心脏的特征。用红细胞悬液对分离的大鼠心脏进行灌注（恒压80 mmHg）。在20分钟的预热期后，开始用10(-8) M异丙肾上腺素灌注3小时（异丙肾上腺素3小时组）或不灌注（对照3小时组），或者立即终止实验（对照0小时组）。分析左心室组织的总CK活性、CK同工酶分布，并通过定量RT-PCR分析B-CK、M-CK、线粒体CK和GAPDH（作为内标）的mRNA。在β-肾上腺素能刺激后（异丙肾上腺素3小时组），而非对照灌注后（对照3小时组），发现B-CK mRNA水平大约增加了三倍，M-CK mRNA水平下降了18%。三组之间的总CK活性以及CK-MM、CK-BB、CK-MB和线粒体CK的分布没有显著差异。因此，β-肾上腺素能刺激诱导了CK基因表达从M-CK向B-CK的转变，这是肥厚和衰竭心脏的特征。这可以被解释为一种适应性机制，在代谢需求增加时使通过CK的能量转导更有效。
