Direct evidence that protein kinase C plays an essential role in the development of late preconditioning against myocardial stunning in conscious rabbits and that epsilon is the isoform involved.

• DOI: 10.1172/jci1258
• Publication Date: 2008-02-11T16:41:47Z
• Authors: Y Qiu; P Ping; X L Tang; S Manchikalapudi; A Rizvi; J Zhang; H Takano; W J Wu; S Teschner; R Bolli
• Keywords: Stunning; Chelerythrine; Myocardial Stunning; Ischemic Preconditioning

Brief ischemic episodes confer marked protection against myocardial stunning 1-3 d later (late preconditioning [PC] stunning). The mechanism of this powerful protective effect is poorly understood. Although protein kinase C (PKC) has been implicated in PC infarction, it unknown whether triggers late stunning. In addition, the entire PKC hypothesis remains controversial, possibly because effects inhibitors on have not correlated with their activity and/or translocation vivo. Thus, conscious rabbits underwent a sequence six 4-min coronary occlusion (O)/4-min reperfusion (R) cycles for three consecutive days (days 1, 2, and 3). control group (group I, n = 7), recovery systolic wall thickening after O/R was markedly improved 2 3 compared day indicating development Administration inhibitor chelerythrine at dose 5 mg/kg before first O 1 II, 10) abrogated stunning, whereas 10-fold lower (0.5 mg/kg; III, 7) did not. 10 min sixth IV, 6) failed to block When were given absence V, 5), severity 24 h modified. Pretreatment phorbol 12-myristate 13-acetate (4 microg/kg) without ischemia VI, 11) induced magnitude equivalent that observed PC. vehicle-treated VIII, caused isoforms epsilon eta from cytosolic particulate fraction significant changes total activity, subcellular distribution or alpha, beta1, beta2, gamma, delta, zeta, iota, lambda, mu isoforms. higher (5 X, 5) prevented both by PC, XI, but epsilon, activation necessary occur To our knowledge, demonstration actually prevents vivo, inhibition results loss protection. Taken together, demonstrate involves PKC-mediated signaling pathway, implicate as specific isoform responsible cardioprotective phenomenon.