This Article Full Text Full Text (PDF) 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Murphy, E. Articles by Steenbergen, C. Search for Related Content PubMed PubMed Citation Articles by Murphy, E. Articles by Steenbergen, C. Related Collections Related Article

(Circulation Research. 2008;103:226.)
© 2008 American Heart Association, Inc.

Editorials

Does Inhibition of Glycogen Synthase Kinase Protect in Mice?

Elizabeth Murphy, Charles Steenbergen

From the Vascular Medicine Branch (E.M.), National Heart, Lung, and Blood Institute, NIH, Bethesda; and Department of Pathology (C.S.), The Johns Hopkins Medical Institutions, Baltimore, Md.

Correspondence to Elizabeth Murphy, Vascular Medicine Branch, NHLBI, NIH, 10 Center Dr, Bethesda, MD 20892. E-mail murphy1@mail.nih.gov

See related article, pages 307–314

Key Words: glycogen synthase kinase • cardioprotection • ischemia • signaling

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Preconditioning (PreC) and postconditioning (PostC) have been shown to initiate a number of signaling cascades that reduce cell death. However, the mechanisms by which these signals reduce cell death have been elusive.¹ PreC has been shown to phosphorylate and thereby inhibit glycogen synthase kinase (GSK)-3β, and perfusion with GSK inhibitors has been shown to reduce cell death induced by ischemia/reperfusion, when added before ischemia² or when added at the start of reperfusion.^3–5 These studies are consistent with data in other tissues showing that inhibition of GSK-3β reduces apoptosis. Information regarding the mechanism by which inhibition of GSK protects has been provided by Juhaszova et al,⁶ who report that inhibition of GSK-3β delays the opening of the mitochondrial permeability transition pore (MPT) (see the Figure). The MPT is a large-conductance pore in the inner mitochondrial membrane which is opened under conditions associated with ischemia/reperfusion, such as high matrix reactive oxygen species and high matrix calcium. Pharmacological inhibitors of the MPT have been shown to reduce ischemia/reperfusion injury, suggesting that activation of MPT might have a role in ischemia/reperfusion-mediated cell death. However the molecular components of the MPT have not been identified.⁷

View larger version (15K):   Figure. Nishino et al8 raise 2 questions: (1) whether inhibition of GSK is required for protection in mice; and (2) whether inhibition of GSK is protective in mouse hearts. PreC and PostC activate a number of redundant signaling pathways that lead to inhibition of MPT. The relative importance of different pathways may vary depending on the model and species. . . . [Full Text of this Article]

Related Article:

Glycogen Synthase Kinase-3 Inactivation Is Not Required for Ischemic Preconditioning or Postconditioning in the Mouse

Yasuhiro Nishino, Ian G. Webb, Sean M. Davidson, Aminul I. Ahmed, James E. Clark, Sebastien Jacquet, Ajay M. Shah, Tetsuji Miura, Derek M. Yellon, Metin Avkiran, and Michael S. Marber
Circ. Res. 2008 103: 307-314. [Abstract] [Full Text] [PDF]

This article has been cited by other articles:

				G. Heusch No RISK, no ... cardioprotection? A critical perspective Cardiovasc Res, November 1, 2009; 84(2): 173 - 175. [Full Text] [PDF]

				J. Musiolik, P. van Caster, A. Skyschally, K. Boengler, P. Gres, R. Schulz, and G. Heusch Reduction of infarct size by gentle reperfusion without activation of reperfusion injury salvage kinases in pigs Cardiovasc Res, August 25, 2009; (2009) cvp271v2. [Abstract] [Full Text] [PDF]

				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]

				A. Skyschally, P. van Caster, K. Boengler, P. Gres, J. Musiolik, D. Schilawa, R. Schulz, and G. Heusch Ischemic Postconditioning in Pigs: No Causal Role for RISK Activation Circ. Res., January 2, 2009; 104(1): 15 - 18. [Abstract] [Full Text] [PDF]