HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 289/6/H2310    most recent 00462.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (16) Citing Articles via Google Scholar Google Scholar Articles by Okada, T. Articles by Imamura, H. Search for Related Content PubMed PubMed Citation Articles by Okada, T. Articles by Imamura, H.

Role of F-actin organization in p38 MAP kinase-mediated apoptosis and necrosis in neonatal rat cardiomyocytes subjected to simulated ischemia and reoxygenation

Cardiovascular Center, Kansai Medical University, Moriguchi City, Japan

Submitted 6 May 2005 ; accepted in final form 15 July 2005

Activation of p38 mitogen-activated protein (MAP) kinase (MAPK) has been implicated in the mechanism of cardiomyocyte (CMC) protection and injury. The p38 MAPK controversy may be related to differential effects of this kinase on apoptosis and necrosis. We have hypothesized that p38 MAPK-mediated F-actin reorganization promotes apoptotic cell death, whereas it protects from osmotic stress-induced necrotic cell death. Cultured neonatal rat CMCs were subjected to 2 h of simulated ischemia followed by reoxygenation. p38 MAPK activity measured by phosphorylation of MAP kinase-activated protein (MAPKAP) kinase 2 was increased during simulated ischemia and reoxygenation. This was associated with translocation of heat shock protein 27 (HSP27) from the cytosolic to the cytoskeletal fraction and F-actin reorganization. Cytochrome c release from mitochondria, caspase-3 activation, and DNA fragmentation were increased during reoxygenation. Robust lactate dehydrogenase (LDH) release was observed under hyposmotic (140 mosM) reoxygenation. The p38 MAPK inhibitor SB-203580 abrogated activation of p38 MAPK, translocation of HSP27, and F-actin reorganization and prevented cytochrome c release, caspase-3 activation, and DNA fragmentation. Conversely, SB-203580 enhanced LDH release during hyposmotic reoxygenation. The F-actin disrupting agent cytochalasin D inhibited F-actin reorganization and prevented cytochrome c release, caspase-3 activation, and DNA fragmentation, whereas it enhanced LDH release during hyposmotic reoxygenation. When CMCs were incubated under the isosmotic condition for the first 15 min of reoxygenation, SB-203580 and cytochalasin D increased ATP content of CMCs and prevented LDH release after the conversion to the hyposmotic condition. These results suggest that F-actin reorganization mediated by activation of p38 MAPK plays a differential role in apoptosis and protection against osmotic stress-induced necrosis during reoxygenation in neonatal rat CMCs; however, the sarcolemmal fragility caused by p38 MAPK inhibition can be reversed during temporary blockade of physical stress during reoxygenation.

mitogen-activated protein kinase; osmotic stress; apoptotic and necrotic cell death

This article has been cited by other articles:

				S. W. Rabkin and M. Y. C. Tsang The action of nitric oxide to enhance cell survival in chick cardiomyocytes is mediated through a cGMP and ERK1/2 pathway while p38 mitogen-activated protein kinase-dependent pathways do not alter cell death Exp Physiol, July 1, 2008; 93(7): 834 - 842. [Abstract] [Full Text] [PDF]

				C. Ballard-Croft, A. C. Locklar, B. J. Keith, R. M. Mentzer Jr, and R. D. Lasley Oxidative stress and adenosine A1 receptor activation differentially modulate subcellular cardiomyocyte MAPKs Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H263 - H271. [Abstract] [Full Text] [PDF]

				Y. Guan, W.-L. Kuo, J. L. Stilwell, H. Takano, A. V. Lapuk, J. Fridlyand, J.-H. Mao, M. Yu, M. A. Miller, J. L. Santos, et al. Amplification of PVT1 Contributes to the Pathophysiology of Ovarian and Breast Cancer Clin. Cancer Res., October 1, 2007; 13(19): 5745 - 5755. [Abstract] [Full Text] [PDF]

				C. D. Venkatakrishnan, A. K. Tewari, L. Moldovan, A. J. Cardounel, J. L. Zweier, P. Kuppusamy, and G. Ilangovan Heat shock protects cardiac cells from doxorubicin-induced toxicity by activating p38 MAPK and phosphorylation of small heat shock protein 27 Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2680 - H2691. [Abstract] [Full Text] [PDF]

				N. Maulik Effect of p38 MAP kinase on cellular events during ischemia and reperfusion: possible therapy Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2302 - H2303. [Full Text] [PDF]