Am J Physiol Cell Physiol Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
QUICK SEARCH:   [advanced]


     

Am J Physiol Cell Physiol (August 4, 2004). doi:10.1152/ajpcell.00144.2004
This Article
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
287/5/C1418    most recent
00144.2004v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Hassouna, A.
Right arrow Articles by Galinanes, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Hassouna, A.
Right arrow Articles by Galinanes, M.
Submitted on March 16, 2004
Accepted on July 8, 2004

PKC {epsilon} is Upstream and PKC {alpha} is Downstream of MitoKATP Channels in the Signal Transduction Pathway of Ischemic Preconditioning of Human Myocardium

Ashraf Hassouna1*, Bashir M Matata1, and Manuel Galinanes1

1 Department of Cardiovascular Sciences, Cardiac Surgery Group, University of Leicester, Leicester, United Kingdom

* To whom correspondence should be addressed. E-mail: hassouna_ashraf{at}hotmail.com.

Background: Protein kinase C (PKC) is involved in the process of ischemic preconditioning (IPC) although the precise mechanism is unknown. Using specific PKC isoforms inhibitors we aim to investigate which PKC isoforms are involved in ischemic preconditioning of the human myocardium and to determine their temporal relationship to mitoKATP channels. Methods: Right atrial muscles sections obtained from patients undergoing cardiac surgery were randomized to receive one of the following protocols: aerobic control, simulated ischemia / reoxygenation, IPC using 5 min simulated ischemia/ 5 min reoxygenation, and finally PKC inhibitors were added 10 min before and 10 min during ischemic preconditioning and then followed by simulated ischemia / reoxygenation. The PKC isoforms inhibitors investigated were V1-2 peptide, GO6976, Rottlerin and LY333531 for PKC {epsilon}, PKC {alpha}, PKC {delta} and PKC {beta} respectively. To investigate the relation of PKC isoforms to mitoKATP channels, PKC {alpha} and {epsilon} isoforms inhibitors, found to be involved in ischemic preconditioning, were added 10 min before and 10 min during preconditioning by diazoxide. CK leakage and MTT cell viability were measured at the end of each protocol. In a third study, phosphorylation of PKC isoforms following activation of the sample by either diazoxide or IPC was detected using western blotting. Results: PKC {alpha} and {epsilon} inhibitors blocked cardioprotection whereas PKC {delta} and {beta} inhibitor did not. The protection elicited by mitoKATP channels opening with diazoxide was blocked by the inhibition by PKC {alpha} but not by inhibition of PKC {epsilon} isoforms. In addition, diazoxide caused increased phosphorylation of PKC {alpha} to a degree similar to ischemic preconditioning but failed to increase PKC {epsilon} phosphorylation. Conclusion: The results demonstrate that PKC {alpha} and {epsilon} are involved in ischemic preconditioning of the human myocardium with PKC {epsilon} being upstream and PKC {alpha} being downstream of mitoKATP channels.




This article has been cited by other articles:


Home page
 Am. J. Physiol. Cell Physiol.Home page
T.-T. Pan, K. L. Neo, L.-F. Hu, Q. C. Yong, and J.-S. Bian
H2S preconditioning-induced PKC activation regulates intracellular calcium handling in rat cardiomyocytes
Am J Physiol Cell Physiol, January 1, 2008; 294(1): C169 - C177.
[Abstract] [Full Text] [PDF]

Home page
 Br J AnaesthHome page
R. A. Bouwman, R. J. P. Musters, B. J. van Beek-Harmsen, J. J. de Lange, R. R. Lamberts, S. A. Loer, and C. Boer
Sevoflurane-induced cardioprotection depends on PKC-{alpha} activation via production of reactive oxygen species
Br. J. Anaesth., November 1, 2007; 99(5): 639 - 645.
[Abstract] [Full Text] [PDF]

Home page
 Anesth. Analg.Home page
M. T. Jiang, Y. Nakae, M. Ljubkovic, W.-M. Kwok, D. F. Stowe, and Z. J. Bosnjak
Isoflurane Activates Human Cardiac Mitochondrial Adenosine Triphosphate-Sensitive K+ Channels Reconstituted in Lipid Bilayers
Anesth. Analg., October 1, 2007; 105(4): 926 - 932.
[Abstract] [Full Text] [PDF]

Home page
 J. Thorac. Cardiovasc. Surg.Home page
C. Kubal, K. Sheth, B. Nadal-Ginard, and M. Galinanes
Bone marrow cells have a potent anti-ischemic effect against myocardial cell death in humans.
J. Thorac. Cardiovasc. Surg., November 1, 2006; 132(5): 1112 - 1118.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Gastrointest. Liver Physiol.Home page
K. Hodges, R. Gill, K. Ramaswamy, P. K. Dudeja, and G. Hecht
Rapid activation of Na+/H+ exchange by EPEC is PKC mediated
Am J Physiol Gastrointest Liver Physiol, November 1, 2006; 291(5): G959 - G968.
[Abstract] [Full Text] [PDF]

Home page
 Circ. Res.Home page
H. Ardehali
Signaling Mechanisms in Ischemic Preconditioning: Interaction of PKC{epsilon} and MitoKATP in the Inner Membrane of Mitochondria
Circ. Res., October 13, 2006; 99(8): 798 - 800.
[Full Text] [PDF]

Home page
 Cardiovasc ResHome page
Z.-Q. Jin and J. S. Karliner
Low dose N, N-dimethylsphingosine is cardioprotective and activates cytosolic sphingosine kinase by a PKC{varepsilon} dependent mechanism
Cardiovasc Res, September 1, 2006; 71(4): 725 - 734.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
M. Nishihara, T. Miura, T. Miki, J. Sakamoto, M. Tanno, H. Kobayashi, Y. Ikeda, K. Ohori, A. Takahashi, and K. Shimamoto
Erythropoietin affords additional cardioprotection to preconditioned hearts by enhanced phosphorylation of glycogen synthase kinase-3beta
Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H748 - H755.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
K. Watanabe, H. Yaoita, K. Ogawa, M. Oikawa, K. Maehara, and Y. Maruyama
Attenuated cardioprotection by ischemic preconditioning in coronary stenosed heart and its restoration by carvedilol
Cardiovasc Res, August 1, 2006; 71(3): 537 - 547.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
G. J. Grover
Mitochondrial ATP-sensitive potassium channels and mitochondrial protein kinase C: sometimes it's good to have a close neighbor
Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1752 - H1753.
[Full Text] [PDF]

Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
M. T. Jiang, M. Ljubkovic, Y. Nakae, Y. Shi, W.-M. Kwok, D. F. Stowe, and Z. J. Bosnjak
Characterization of human cardiac mitochondrial ATP-sensitive potassium channel and its regulation by phorbol ester in vitro
Am J Physiol Heart Circ Physiol, May 1, 2006; 290(5): H1770 - H1776.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
A. Hassouna, M. Loubani, B. M. Matata, A. Fowler, N. B. Standen, and M. Galinanes
Mitochondrial dysfunction as the cause of the failure to precondition the diabetic human myocardium
Cardiovasc Res, February 1, 2006; 69(2): 450 - 458.
[Abstract] [Full Text] [PDF]

Home page
 Anesth. Analg.Home page
L. A. Turner, K. Fujimoto, A. Suzuki, A. Stadnicka, Z. J. Bosnjak, and W.-M. Kwok
The Interaction of Isoflurane and Protein Kinase C-Activators on Sarcolemmal KATP Channels
Anesth. Analg., June 1, 2005; 100(6): 1680 - 1686.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH
Visit Other APS Journals Online
Copyright © 1977 by the American Physiological Society.