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: 286/3/H847    most recent 00715.2003v1 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 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 Web of Science (24) Citing Articles via Google Scholar Google Scholar Articles by Morrison, L. E. Articles by Glembotski, C. C. Search for Related Content PubMed PubMed Citation Articles by Morrison, L. E. Articles by Glembotski, C. C.

Roles for B-crystallin and HSPB2 in protecting the myocardium from ischemia-reperfusion-induced damage in a KO mouse model

¹San Diego State University Heart Institute and The Department of Biology, San Diego State University, San Diego, California 92182; and ²National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892-2730

Submitted 24 July 2003 ; accepted in final form 21 October 2003

Overexpression studies have shown that the small heat shock proteins (sHSP) protect the myocardium from ischemia-reperfusion (I/R)-induced damage. However, gene deletion studies are necessary to demonstrate whether sHSPs are required for protection. The genes for B-crystallin (BC) and HSPB2, two sHSPs that are expressed in high levels in the heart, are in close proximity to one another; as a result, both genes were disrupted in a recently generated knockout (KO) mouse line. The BC/HSPB2 KO mouse line is currently the only model that features disruption of sHSPs normally expressed in the heart. Accordingly, we examined the cardiac morphology, function, and response to I/R-induced stress in BC-HSPB2 KO mice. Initial gross, light microscopic and echocardiographic characterization showed that the morphological and functional properties of hearts from adult KO mice were indistinguishable from age-matched wild-type (WT) mice. Electron microscopy showed that, compared with WT mouse hearts, KO mouse heart sarcomeres were relatively normal. Isolated perfused KO mouse hearts displayed normal contractility; however, when compared with WT, after I/R, KO mouse hearts exhibited a twofold reduction in contractile recovery, as well as increased necrosis and apoptosis. Additionally, when compared with WT, KO mouse hearts exhibited 43% less reduced glutathione, which is known to protect from I/R-induced damage. Thus, whereas neither BC nor HSPB2 is essential for myocardial development and function under nonstressful conditions, one or both are required for maximal functional recovery and protection from I/R-induced necrosis and apoptosis.

small heat shock protein; necrosis; apoptosis; glutathione; knockout mouse

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. R.K. Kumarapeli, H. Su, W. Huang, M. Tang, H. Zheng, K. M. Horak, M. Li, and X. Wang {alpha}B-Crystallin Suppresses Pressure Overload Cardiac Hypertrophy Circ. Res., December 5, 2008; 103(12): 1473 - 1482. [Abstract] [Full Text] [PDF]

				I. Pinz, J. Robbins, N. S. Rajasekaran, I. J. Benjamin, and J. S. Ingwall Unmasking different mechanical and energetic roles for the small heat shock proteins CryAB and HSPB2 using genetically modified mouse hearts FASEB J, January 1, 2008; 22(1): 84 - 92. [Abstract] [Full Text] [PDF]

				J.-K. Jin, R. Whittaker, M. S. Glassy, S. B. Barlow, R. A. Gottlieb, and C. C. Glembotski Localization of phosphorylated {alpha}B-crystallin to heart mitochondria during ischemia-reperfusion Am J Physiol Heart Circ Physiol, January 1, 2008; 294(1): H337 - H344. [Abstract] [Full Text] [PDF]

				R. T. Clements, N. R. Sodha, J. Feng, S. Mieno, M. Boodhwani, B. Ramlawi, C. Bianchi, and F. W. Sellke Phosphorylation and translocation of heat shock protein 27 and alphaB-crystallin in human myocardium after cardioplegia and cardiopulmonary bypass. J. Thorac. Cardiovasc. Surg., December 1, 2007; 134(6): 1461 - 1470.e3. [Abstract] [Full Text] [PDF]

				I. J. Benjamin, Y. Guo, S. Srinivasan, S. Boudina, R. P. Taylor, N. S. Rajasekaran, R. Gottlieb, E. F. Wawrousek, E. D. Abel, and R. Bolli CRYAB and HSPB2 deficiency alters cardiac metabolism and paradoxically confers protection against myocardial ischemia in aging mice Am J Physiol Heart Circ Physiol, November 1, 2007; 293(5): H3201 - H3209. [Abstract] [Full Text] [PDF]

				O. Zolk, C. Schenke, and A. Sarikas The ubiquitin-proteasome system: Focus on the heart Cardiovasc Res, June 1, 2006; 70(3): 410 - 421. [Abstract] [Full Text] [PDF]

				V. Morozov and E. F. Wawrousek Caspase-dependent secondary lens fiber cell disintegration in {alpha}A-/{alpha}B-crystallin double-knockout mice Development, March 1, 2006; 133(5): 813 - 821. [Abstract] [Full Text] [PDF]

				M. Horowitz, L. Eli-Berchoer, I. Wapinski, N. Friedman, and E. Kodesh Stress-related genomic responses during the course of heat acclimation and its association with ischemic-reperfusion cross-tolerance J Appl Physiol, October 1, 2004; 97(4): 1496 - 1507. [Abstract] [Full Text] [PDF]