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: 292/5/H2227    most recent 01091.2006v1 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 (17) Citing Articles via Google Scholar Google Scholar Articles by Fülöp, N. Articles by Chatham, J. C. Search for Related Content PubMed PubMed Citation Articles by Fülöp, N. Articles by Chatham, J. C.

Glucosamine cardioprotection in perfused rat hearts associated with increased O-linked N-acetylglucosamine protein modification and altered p38 activation

Departments of ¹Medicine, ²Physiology, and ³Cell Biology, University of Alabama at Birmingham, Birmingham, Alabama

Submitted 5 October 2006 ; accepted in final form 27 December 2006

We have shown that, in the perfused heart, glucosamine improved functional recovery following ischemia and that this appeared to be mediated via an increase in O-linked N-acetylglucosamine (O-GlcNAc) levels on nucleocytoplasmic proteins. Several kinase pathways, specifically Akt and the mitogen-activated protein kinases (MAPKs) p38 and ERK1/2, which have been implicated in ischemic cardioprotection, have also been reported to be modified in response to increased O-GlcNAc levels. Therefore, the goals of this study were to determine the effect of ischemia on O-GlcNAc levels and to evaluate whether the cardioprotection resulting from glucosamine treatment could be attributed to changes in ERK1/2, Akt, and p38 phosphorylation. Isolated rat hearts were perfused with or without 5 mM glucosamine and were subjected to 5, 10, or 30 min of low-flow ischemia or 30 min of low-flow ischemia and 60 min of reperfusion. Glucosamine treatment attenuated ischemic contracture and improved functional recovery at the end of reperfusion. Glucosamine treatment increased flux through the hexosamine biosynthesis pathway and increased O-GlcNAc levels but had no effect on ATP levels. Glucosamine did not alter the response of either ERK1/2 or Akt to ischemia-reperfusion; however, it significantly attenuated the ischemia-induced increase in p38 phosphorylation and paradoxically increased p38 phosphorylation at the end of reperfusion. These data support the notion that O-GlcNAc may play an important role as an internal stress response and that glucosamine-induced cardioprotection may be mediated via the p38 MAPK pathway.

hexosamine biosynthesis; mitogen-activated protein kinase; Akt; ischemia

This article has been cited by other articles:

				L. Hue and H. Taegtmeyer The Randle cycle revisited: a new head for an old hat Am J Physiol Endocrinol Metab, September 1, 2009; 297(3): E578 - E591. [Abstract] [Full Text] [PDF]

				L. Zou, S. Yang, V. Champattanachai, S. Hu, I. H. Chaudry, R. B. Marchase, and J. C. Chatham Glucosamine improves cardiac function following trauma-hemorrhage by increased protein O-GlcNAcylation and attenuation of NF-{kappa}B signaling Am J Physiol Heart Circ Physiol, February 1, 2009; 296(2): H515 - H523. [Abstract] [Full Text] [PDF]

				B. Laczy, B. G. Hill, K. Wang, A. J. Paterson, C. R. White, D. Xing, Y.-F. Chen, V. Darley-Usmar, S. Oparil, and J. C. Chatham Protein O-GlcNAcylation: a new signaling paradigm for the cardiovascular system Am J Physiol Heart Circ Physiol, January 1, 2009; 296(1): H13 - H28. [Abstract] [Full Text] [PDF]

				G. A. Ngoh and S. P. Jones New Insights into Metabolic Signaling and Cell Survival: The Role of {beta}-O-Linkage of N-Acetylglucosamine J. Pharmacol. Exp. Ther., December 1, 2008; 327(3): 602 - 609. [Abstract] [Full Text] [PDF]

				K. D. Singleton and P. E. Wischmeyer Glutamine Induces Heat Shock Protein Expression Via O-Glycosylation and Phosphorylation of HSF-1 and Sp1 JPEN J Parenter Enteral Nutr, July 1, 2008; 32(4): 371 - 376. [Abstract] [Full Text] [PDF]

				D. Xing, W. Feng, L. G. Not, A. P. Miller, Y. Zhang, Y.-F. Chen, E. Majid-Hassan, J. C. Chatham, and S. Oparil Increased protein O-GlcNAc modification inhibits inflammatory and neointimal responses to acute endoluminal arterial injury Am J Physiol Heart Circ Physiol, July 1, 2008; 295(1): H335 - H342. [Abstract] [Full Text] [PDF]

				V. Champattanachai, R. B. Marchase, and J. C. Chatham Glucosamine protects neonatal cardiomyocytes from ischemia-reperfusion injury via increased protein O-GlcNAc and increased mitochondrial Bcl-2 Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1509 - C1520. [Abstract] [Full Text] [PDF]

				J. Liu, R. B. Marchase, and J. C. Chatham Increased O-GlcNAc levels during reperfusion lead to improved functional recovery and reduced calpain proteolysis Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1391 - H1399. [Abstract] [Full Text] [PDF]

				N. E. Zachara The sweet nature of cardioprotection Am J Physiol Heart Circ Physiol, September 1, 2007; 293(3): H1324 - H1326. [Full Text] [PDF]

				N. K. LeBrasseur, T.-A. S. Duhaney, D. S. De Silva, L. Cui, P. C. Ip, L. Joseph, and F. Sam Effects of Fenofibrate on Cardiac Remodeling in Aldosterone-Induced Hypertension Hypertension, September 1, 2007; 50(3): 489 - 496. [Abstract] [Full Text] [PDF]