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Role of glycogen synthase kinase following myocardial infarction and ischemia–reperfusion

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Abstract

Glycogen synthase kinase-3 beta (GSK3β) is principally is a glycogen synthase phosphorylating enzyme that is well known for its role in muscle metabolism. GSK3β is a serine/threonine protein Kinase, which is responsible for several essential roles in mammalian cells. This enzyme is implicated in the pathophysiology of many conditions involved in homeostasis and cellular immigration. GSK3β is involved in several pathways leading to neurodegenerative diseases such as Alzheimer’s disease and Parkinson’s disease. Increasing evidence has shown the potential importance of GSK3β in ischemic heart disease and ischemia–reperfusion pathologies. Reperfusion injury may occur in tissues after prolonged ischemia following reperfusion. Reperfusion injury can be life threatening. Reperfusion injury occurs due to a change in ionic homeostasis, excess free radical production, mitochondrial damage and cell death. There are however clear, cardiac-protective signals; although the molecular pathophysiology is not clearly understood. In normal physiology, GSK3β has a critical role in the cytoprotective pathway. However, it`s controversial role in ischemia and ischemia–reperfusion is a topic of current interest. In this review, we have opted to focus on GSK3β interactions with mitochondria in ischemic heart disease and expand on the therapeutic interventions.

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Abbreviations

IGF1:

Insulin growth factor I

SRF:

Serum response factor

CK1:

Casein kinase

TAO:

TAO kinase-1

p38MAPK:

Mitogen-activated protein kinase

PI3K:

Phosphatidylinositol-4,5-bisphosphate-3-kinase

AKT:

Serin/threonine kinase-1

MPTP:

Mitochondrial permeability transition pores

cypD:

Cyclophilin D-dependent mitochondrial permeability transition

ANT :

ADP/ATP translocase 3

VDAC :

Voltage-dependent anion-selective channel protein 1

BAX :

BCL2 associated X apoptosis regulator

BCL-2:

BCL2 apoptosis regulator

Cyto c:

Cytochrome c

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    Authors and Affiliations

    1. Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

      S. Ghaderi & B. Baradaran

    2. Department of Molecular Medicine, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

      S. Ghaderi

    3. Department of Clinical Biochemistry and Laboratory Medicine, Faculty of Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

      N. Alidadiani

    4. Swansea University Medical School, Swansea University, Swansea, UK

      N. Dilaver

    5. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

      H. R. Heidari

    6. Department of Cardiothoracic Surgery, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

      R. Parvizi

    7. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

      R. Rahbarghazi

    8. Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

      R. Rahbarghazi

    9. Department of Anatomy, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran

      J. Soleimani-Rad

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    S. Ghaderi, N. Alidadiani, J. Soleimani-Rad and B. Baradaran have contributed equally to this work.

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    Ghaderi, S., Alidadiani, N., Dilaver, N. et al. Role of glycogen synthase kinase following myocardial infarction and ischemia–reperfusion. Apoptosis 22, 887–897 (2017). https://doi.org/10.1007/s10495-017-1376-0

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