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: 293/4/H2056    most recent 00403.2007v1 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 (12) Citing Articles via Google Scholar Google Scholar Articles by Korzick, D. H. Articles by Saupe, K. W. Search for Related Content PubMed PubMed Citation Articles by Korzick, D. H. Articles by Saupe, K. W.

CALL FOR PAPERS
Cardiovascular Aging

Local delivery of PKC-activating peptide mimics ischemic preconditioning in aged hearts through GSK-3 but not F₁-ATPase inactivation

¹Intercollege Program in Physiology and ²Department of Kinesiology, Pennsylvania State University, University Park, Pennsylvania; and ³Department of Medicine, University of Wisconsin, Madison, Wisconsin

Submitted 31 March 2007 ; accepted in final form 2 August 2007

In adult heart, selective PKC activation limits ischemia (I)-reperfusion (R) damage and mimics the protection associated with ischemic preconditioning. We sought to determine whether local delivery of PKC activator peptide -receptor for activated C-kinase (-RACK) is sufficient to produce a similarly protected phenotype in aged hearts. Langendorff-perfused hearts isolated from adult (5 mo; n = 9) and aged (24 mo; n = 9) male Fisher 344 rats were perfused with -RACK conjugated to Tat (500 nM) or Tat only (500 nM) for 10 min before global 31-min ischemia. Western blotting was used to measure mitochondrial targeting of PKC, PKC, phospho (p)-GSK-3 (Ser⁹) and GSK-3 in hearts snap-frozen during I. Recovery of left ventricular developed pressure was significantly improved by -RACK (P < 0.01) and infarct size reduced in 24-mo rats vs. age-matched controls (60% vs. 34%; P < 0.01). Mitochondrial PKC levels were 30% greater during I with -RACK in aged vs. control rats (P < 0.01). Interestingly, mitochondrial GSK-3 levels were threefold greater in aged vs. adult rats during I, and -RACK prevented this increase (P < 0.01). Mitochondrial p-GSK-3 levels were also greater in aged rats after -RACK (P < 0.01), and subsequent inhibition of GSK-3 with SB-216763 (3 µM) before I/R elicited protection similar to that of -RACK (n = 3/group). Mitochondrial proteomic analysis further identified group differences in the F₁-ATPase -subunit, and coimmunoprecipitation studies revealed a novel interaction with PKC. F₁-ATPase-PKC association was affected by -RACK in adult but not aged rats. Our results provide evidence, for the first time, for PKC-mediated protection in aged rat heart after I/R and suggest a central role for mitochondrial GSK-3 but not F₁-ATPase as a potential target of PKC to limit I/R damage with aging.

ischemia-reperfusion injury; proteomics; mitochondria; senescence

This article has been cited by other articles:

				M. Juhaszova, D. B. Zorov, Y. Yaniv, H. B. Nuss, S. Wang, and S. J. Sollott Role of Glycogen Synthase Kinase-3{beta} in Cardioprotection Circ. Res., June 5, 2009; 104(11): 1240 - 1252. [Abstract] [Full Text] [PDF]

				J. N. Peart and J. P. Headrick Clinical cardioprotection and the value of conditioning responses Am J Physiol Heart Circ Physiol, June 1, 2009; 296(6): H1705 - H1720. [Abstract] [Full Text] [PDF]

				Y. Murozono, N. Takahashi, T. Shinohara, T. Ooie, Y. Teshima, M. Hara, T. Saikawa, and H. Yoshimatsu Hyperthermia-Induced Cardioprotection Is Potentiated by Ischemic Postconditioning in Rats Experimental Biology and Medicine, May 1, 2009; 234(5): 573 - 581. [Abstract] [Full Text] [PDF]

				V. Akoyev, S. Das, S. Jena, L. Grauer, and D. J. Takemoto Hypoxia-Regulated Activity of PKC{epsilon} in the Lens Invest. Ophthalmol. Vis. Sci., March 1, 2009; 50(3): 1271 - 1282. [Abstract] [Full Text] [PDF]

				T. Nguyen, M. Ogbi, and J. A. Johnson Delta Protein Kinase C Interacts with the d Subunit of the F1F0 ATPase in Neonatal Cardiac Myocytes Exposed to Hypoxia or Phorbol Ester: IMPLICATIONS FOR F1F0 ATPase REGULATION J. Biol. Chem., October 31, 2008; 283(44): 29831 - 29840. [Abstract] [Full Text] [PDF]

				P. Zhai and J. Sadoshima Overcoming an Energy Crisis?: An Adaptive Role of Glycogen Synthase Kinase-3 Inhibition in Ischemia/Reperfusion Circ. Res., October 24, 2008; 103(9): 910 - 913. [Full Text] [PDF]

				A. V. G. Edwards, M. Y. White, and S. J. Cordwell The Role of Proteomics in Clinical Cardiovascular Biomarker Discovery Mol. Cell. Proteomics, October 1, 2008; 7(10): 1824 - 1837. [Abstract] [Full Text] [PDF]

				J. D. O'Brien and S. E. Howlett Simulated ischemia-induced preconditioning of isolated ventricular myocytes from young adult and aged Fischer-344 rat hearts Am J Physiol Heart Circ Physiol, August 1, 2008; 295(2): H768 - H777. [Abstract] [Full Text] [PDF]