| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
1 Cardiovascular Center, Kansai Medical University, Moriguchi, Japan
* To whom correspondence should be addressed. E-mail: otanih{at}takii.kmu.ac.jp.
Activation of p38MAP kinase (p38MAPK) has been implicated in the mechanism of cardiomyocytes (CMCs) protection and injury. The p38MAPK controversy may be related to differential effects of this kinase on apoptosis and necrosis. We have hypothesized that p38MAPK-mediated F-actin reorganization promotes apoptotic cell death, while it protects from osmotic stress-induced necrotic cell death. Cultured neonatal rat CMCs were subjected to 2 hours of simulated ischemia followed by reoxygenation. p38MAPK activity measured by phosphorylation of MAPKAPK-2 was increased during simulated ischemia and reoxygenation. This was associated with translocation of 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 LDH release was observed under hyposmotic (140 mosm) reoxygenation. The p38MAPK inhibitor SB203580 abrogated activation of p38MAPK, translocation of HSP27, and F-actin reorganization and prevented cytochrome c release, caspase 3 activation, and DNA fragmentation. Conversely, SB203580 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, while it enhanced LDH release during hyposmotic reoxygenation. When CMCs were incubated under the isosmotic condition for the first 15 minutes of reoxygenation, SB203580 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 p38MAPK plays a differential role in apoptosis and protection against osmotic stress-induced necrosis during reoxygenation in neonatal rat CMCs, however, that the sarcolemmal fragility caused by p38MAPK inhibition can be reversed during temporary blockade of physical stress during reoxygenation.
This article has been cited by other articles:
|
|
 |
|
  R. Whittaker, M. S. Glassy, N. Gude, M. A. Sussman, R. A. Gottlieb, and C. C. Glembotski Kinetics of the translocation and phosphorylation of {alpha}B-crystallin in mouse heart mitochondria during ex vivo ischemia Am J Physiol Heart Circ Physiol, May 1, 2009; 296(5): H1633 - H1642. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. C. P. Thirone, P. Speight, M. Zulys, O. D. Rotstein, K. Szaszi, S. F. Pedersen, and A. Kapus Hyperosmotic stress induces Rho/Rho kinase/LIM kinase-mediated cofilin phosphorylation in tubular cells: key role in the osmotically triggered F-actin response Am J Physiol Cell Physiol, March 1, 2009; 296(3): C463 - C475. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
