© 2001 by European Society of Cardiology
Copyright © 2000, European Society of Cardiology
Direct activation of mitochondrial KATP channels mimics preconditioning but protein kinase C activation is less effective in middle-aged rat hearts
Department of Geriatrics, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-Ku, Tokyo 160-8582, Japan
* Corresponding author. Tel.: +81-3-3353-1211; fax: +81-3-5269-2468 masatota{at}mc.med.keio.ac.jp
Objectives: This study is aimed to determine whether loss of preconditioning (IP) effects in the middle-aged hearts (MA) is due to the failure of protein kinase C (PKC) activation and, if so, whether direct activation of mitochondrial ATP-sensitive potassium channels (m-KATP) or PKC mimics IP. Background: PKC is a mediator and m-KATP may be its downstream effector of IP in young adult hearts (YA), but we have demonstrated that IP is not effective in MA. Methods and results: Isolated hearts from YA (12-week) and MA (50-week) Fischer 344 rats were preconditioned by three cycles of ischemia and reperfusion (5 min each), and the translocation of PKC isoforms and the effects on reperfusion injury were assessed. In some hearts activation of m-KATP or PKC by diazoxide or 1,2-dioctanoyl glycerol (DOG) was performed before 25 min of global ischemia/30 min of reperfusion. IP could improve the recovery of LV function and resulted in higher content of ATP after reperfusion in YA but these beneficial effects of IP was not found in MA. The effects of IP in YA were abolished by 5-hydroxydecanoate. In YA but not in MA, immunohistochemical analysis revealed that IP translocated PKC-
and 
from the cytosolic or membrane to the perinuclear region but immunoblotting analysis showed translocation of PKC-, and 
to the membrane fraction. Pretreatment with diazoxide or DOG mimicked IP and decreased the creatine kinase release in YA. Diazoxide was also effective but effects of DOG were less in MA as compared with in YA. Conclusions: IP is not effective in MA hearts partly due to failure of translocation of PKC isoforms. Moreover, less efficacy of PKC activation by DOG as compared with activities of m-KATP by diazoxide in MA may suggest that defect(s) of cell signaling downstream to PKC may also be involved in the loss of IP effects in MA.
KEYWORDS ATP, adenosine triphosphate; CK, creatine kinase; DOG, 1,2-dioctanoyl-sn-glycerol; dP/dt, the first derivative of left ventricular pressure; 5HD, 5-hydroxydecanoate; IP, ischemic preconditioning; KATP, ATP-sensitive potassium channel(s); LVDP, left ventricular developed pressure; LVEDP, left ventricular end-diastolic pressure; PKC, protein kinase C
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Boengler, R. Schulz, and G. Heusch Loss of cardioprotection with ageing Cardiovasc Res, July 15, 2009; 83(2): 247 - 261. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. N. Peart and J. P. Headrick Clinical cardioprotection and the value of conditioning responses Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1705 - H1720. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Shinmura, M. Nagai, K. Tamaki, and R. Bolli Loss of ischaemic preconditioning in ovariectomized rat hearts: possible involvement of impaired protein kinase C {varepsilon} phosphorylation Cardiovasc Res, August 1, 2008; 79(3): 387 - 394. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. Tanaka-Esposito, Q. Chen, S. Moghaddas, and E. J. Lesnefsky Ischemic preconditioning does not protect via blockade of electron transport J Appl Physiol, August 1, 2007; 103(2): 623 - 628. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Hunter, J. C. Kostyak, J. L. Novotny, A. M. Simpson, and D. H. Korzick Estrogen deficiency decreases ischemic tolerance in the aged rat heart: roles of PKC{delta}, PKC{epsilon}, Akt, and GSK3beta Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R800 - R809. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Chen, A. K. S. Camara, D. F. Stowe, C. L. Hoppel, and E. J. Lesnefsky Modulation of electron transport protects cardiac mitochondria and decreases myocardial injury during ischemia and reperfusion Am J Physiol Cell Physiol, January 1, 2007; 292(1): C137 - C147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Juhaszova, C. Rabuel, D. B. Zorov, E. G. Lakatta, and S. J. Sollott Protection in the aged heart: preventing the heart-break of old age? Cardiovasc Res, May 1, 2005; 66(2): 233 - 244. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. Willems, K. J. Ashton, and J. P. Headrick Adenosine-mediated cardioprotection in the aging myocardium Cardiovasc Res, May 1, 2005; 66(2): 245 - 255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Przyklenk, G. Li, B. Z. Simkhovich, and R. A. Kloner Mechanisms of myocardial ischemic preconditioning are age related: PKC-{epsilon} does not play a requisite role in old rabbits J Appl Physiol, December 1, 2003; 95(6): 2563 - 2569. [Abstract] [Full Text]
|
|
|
|
 |
|
 M. Zaugg, E. Lucchinetti, C. Garcia, T. Pasch, D. R. Spahn, and M. C. Schaub Anaesthetics and cardiac preconditioning. Part II. Clinical implications Br. J. Anaesth., October 1, 2003; 91(4): 566 - 576. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Loubani, S. Ghosh, and M. Galinanes The aging human myocardium: tolerance to ischemia and responsiveness to ischemic preconditioning J. Thorac. Cardiovasc. Surg., July 1, 2003; 126(1): 143 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P Headrick, L. Willems, K. J Ashton, K. Holmgren, J. Peart, and G P. Matherne Ischaemic tolerance in aged mouse myocardium: the role of adenosine and effects of A1 adenosine receptor overexpression J. Physiol., June 15, 2003; 549(3): 823 - 833. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Abete, G. Testa, N. Ferrara, D. De Santis, P. Capaccio, L. Viati, C. Calabrese, F. Cacciatore, G. Longobardi, M. Condorelli, et al. Cardioprotective effect of ischemic preconditioning is preserved in food-restricted senescent rats Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H1978 - H1987. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T.-M. Lee, S.-F. Su, T.-F. Chou, Y.-T. Lee, and C.-H. Tsai Loss of Preconditioning by Attenuated Activation of Myocardial ATP-Sensitive Potassium Channels in Elderly Patients Undergoing Coronary Angioplasty Circulation, January 22, 2002; 105(3): 334 - 340. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Przyklenk, G. Li, and P. Whittaker No loss in the in vivo efficacy of ischemic preconditioning in middle-aged and old rabbits J. Am. Coll. Cardiol., November 15, 2001; 38(6): 1741 - 1747. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Schulman, D. S. Latchman, and D. M. Yellon Effect of aging on the ability of preconditioning to protect rat hearts from ischemia-reperfusion injury Am J Physiol Heart Circ Physiol, October 1, 2001; 281(4): H1630 - H1636. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Pepe Dysfunctional ischemic preconditioning mechanisms in aging Cardiovasc Res, January 1, 2001; 49(1): 11 - 14. [Full Text] [PDF]
|
|
|
|
|
|
P. Abete, G. Testa, N. Ferrara, D. De Santis, P. Capaccio, L. Viati, C. Calabrese, F. Cacciatore, G. Longobardi, M. Condorelli, et al. Cardioprotective effect of ischemic preconditioning is preserved in food-restricted senescent rats Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H1978 - H1987. [Abstract] [Full Text] [PDF]
|
|