Role of glycogen synthase kinase-3β in cardioprotection

Magdalena Juhaszova, Dmitry B. Zorov, Yael Yaniv, H. Bradley Nuss, Su Wang, Steven J. Sollott

Research output: Contribution to journalArticle

Abstract

Limitation of infarct size by ischemic/pharmacological pre- and postconditioning involves activation of a complex set of cell-signaling pathways. Multiple lines of evidence implicate the mitochondrial permeability transition pore (mPTP) as a key end effector of ischemic/pharmacological pre- and postconditioning. Increasing the ROS threshold for mPTP induction enhances the resistance of cardiomyocytes to oxidant stress and results in infarct size reduction. Here, we survey and synthesize the present knowledge about the role of glycogen synthase kinase (GSK)-3β in cardioprotection, including pre- and postconditioning. Activation of a wide spectrum of cardioprotective signaling pathways is associated with phosphorylation and inhibition of a discrete pool of GSK-3β relevant to mitochondrial signaling. Therefore, GSK-3β has emerged as the integration point of many of these pathways and plays a central role in transferring protective signals downstream to target(s) that act at or in proximity to the mPTP. Bcl-2 family proteins and mPTP-regulatory elements, such as adenine nucleotide translocator and cyclophilin D (possibly voltage-dependent anion channel), may be the functional downstream target(s) of GSK-3β. Gaining a better understanding of these interactions to control and prevent mPTP induction when appropriate will enable us to decrease the negative impact of the reperfusion-induced ROS burst on the fate of mitochondria and perhaps allow us to limit propagation of damage throughout and between cells and consequently, to better limit infarct size.

Original languageEnglish (US)
Pages (from-to)1240-1252
Number of pages13
JournalCirculation Research
Volume104
Issue number11
DOIs
StatePublished - Jun 5 2009
Externally publishedYes

Keywords

  • Mitochondria
  • Permeability transition pore
  • ROS-induced ROS release

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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  • Cite this

    Juhaszova, M., Zorov, D. B., Yaniv, Y., Nuss, H. B., Wang, S., & Sollott, S. J. (2009). Role of glycogen synthase kinase-3β in cardioprotection. Circulation Research, 104(11), 1240-1252. https://doi.org/10.1161/CIRCRESAHA.109.197996