Acute changes of myocardial creatine kinase gene expression under beta-adrenergic stimulation.
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.
Hammerschmidt
S
S
Department of Medicine Pharmacology, University of Würzburg, Würzburg, Germany. stefan.hammerschmidt@t-online.de
Bell
M
M
Büchler
N
N
Wahn
H
H
Remkes
H
H
Lohse
M J
MJ
Neubauer
S
S
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D006332:Cardiomegaly / Q000378:metabolism; D003402:Creatine Kinase / Q000032:analysis / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D009206:Myocardium / Q000201:enzymology*; D010477:Perfusion; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D016277:Ventricular Function, Left
D000318:Adrenergic beta-Agonists; D007527:Isoenzymes; D012333:RNA, Messenger; D003402:Creatine Kinase; D007545:Isoproterenol