Ischemic preconditioning triggers the activation of MAP kinases and MAPKAP kinase 2 in rat hearts

FEBS Letters

Das, Dipak K.¹  Watanabe, Masazumi¹  Huang, Chi-Kuang²  Maulik, Nilanjana¹  Schley, James A.¹  Cordis, Gerald A.¹  Zu, You-Li² 

[1] Cardiovascular Division, Department of Surgery, University of Connecticut School of Medicine, Farmington, CT 06030-1110, USA;Department of Pathology, University of Connecticut School of Medicine, Farmington, CT 06030-1110, USA

关键词: Ischemia/reperfusion;    Stress adaptation;    Tyrosine kinase;    MAP kinase;    MAPKAP kinase 2;    Phospholipase D;    Signal transduction;    Heart;   

DOI  :  10.1016/0014-5793(96)01109-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

While much is known about the beneficial effects of myocardial stress adaptation, relatively less information is available about the adaptive mechanisms. To explore the signaling pathways of stress adaptation, isolated working rat hearts were divided into three groups. Group I was adapted to stress by conventional technique of repeated ischemia and reperfusion consisting of 5 min of ischemia followed by 10 min of reperfusion, repeated four times. Group II was treated with 100 μM of genistein, a tyrosine kinase inhibitor, followed by preconditioning as described for group I. The third group, perfused with buffer only for 60 min, served as control. All hearts were subjected to 30 min of ischemia followed by 30 min of reperfusion. The results of our study demonstrated better postischemic myocardial functions in the preconditioned hearts as evidenced by increased aortic flow, coronary flow, developed pressure and lesser amount of tissue injury as evidenced by the decreased creatine kinase release. The preconditioning effects were associated with enhancement of phospholipase D activity in the heart. The preconditioning effect was almost abolished by the genistein treatment which also prevented the enhancement of phospholipase D activities. Additionally, preconditioning of the rat hearts stimulated protein kinase C, MAP kinase, and MAPKAP kinase 2 activities which were inhibited by genistein. The results identifies for the first time tyrosine kinase-phospholipase D as potential signaling pathway for ischemic preconditioning, and implicates the involvement of multiple protein kinases in myocardial adaptation to ischemia.

【 授权许可】

Unknown