Cardioprotection by adaptation to ischaemia augments autophagy in association with BAG-1 protein

Narasimman Gurusamy, I. Lekli, Nikolai V. Gorbunov, Mihaela Gherghiceanu, Lawrence M. Popescu, Dipak K. Das

Research output: Contribution to journalArticle

110 Citations (Scopus)

Abstract

Autophagy is an intracellular process in which a cell digests its own constituents via lysosomal degradative pathway. Though autophagy has been shown in several cardiac diseases like heart failure, hypertrophy and ischaemic cardiomyopathy, the role and the regulation of autophagy is still largely unknown. Bcl-2-associated athanogene (BAG-1) is a multifunctional pro-survival molecule that binds with Hsp70/Hsc70. In this study, myocardial adaptation to ischaemia by repeated brief episodes of ischaemia and reperfusion (I/R) prior to lethal I/R enhanced the expression of autophagosomal membrane specific protein light chain 3 (LC3)-II, and Beclin-1, a molecule involved in autophagy and BAG-1. Autophagosomes structures were found in the adapted myocardium through electron microscopy. Co-immunoprecipitation and co-immunofluorescence analyses revealed that LC3-II was bound with BAG-1. Inhibition of autophagy by treating rats with Wortmannin (15 μg/kg; intraperitoneally) abolished the ischaemic adaptation-induced induction of LC3-II, Beclin-1, BAG-1 and cardioprotection. Intramyocardial injection of BAG-1 siRNA attenuated the induction of LC3-II, and abolished the cardioprotection achieved by adaptation. Furthermore, hypoxic adaptation in cardiac myoblast cells induced LC3-II and BAG-1. BAG-1 siRNA treatment attenuated hypoxic adaptation-induced LC3-II and BAG-1, and abolished improvement in cardiac cell survival and reduction of cell death. These results clearly indicate that myocardial protection elicited by adaptation is mediated at least in part via up-regulation of autophagy in association with BAG-1 protein.

Original languageEnglish
Pages (from-to)373-387
Number of pages15
JournalJournal of Cellular and Molecular Medicine
Volume13
Issue number2
DOIs
Publication statusPublished - Feb 2009

Fingerprint

Autophagy
Ischemia
Light
Small Interfering RNA
Reperfusion
Cardiac Myoblasts
Ocular Adaptation
Cardiomegaly
Cardiomyopathies
Immunoprecipitation
Fluorescent Antibody Technique
BCL2-associated athanogene 1 protein
Heart Diseases
Cell Survival
Myocardium
Electron Microscopy
Membrane Proteins
Cell Death
Up-Regulation
Heart Failure

Keywords

  • Autophagy
  • BAG-1
  • Cardiac adaptation
  • Ischaemia
  • Reperfusion

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Cardioprotection by adaptation to ischaemia augments autophagy in association with BAG-1 protein. / Gurusamy, Narasimman; Lekli, I.; Gorbunov, Nikolai V.; Gherghiceanu, Mihaela; Popescu, Lawrence M.; Das, Dipak K.

In: Journal of Cellular and Molecular Medicine, Vol. 13, No. 2, 02.2009, p. 373-387.

Research output: Contribution to journalArticle

Gurusamy, Narasimman ; Lekli, I. ; Gorbunov, Nikolai V. ; Gherghiceanu, Mihaela ; Popescu, Lawrence M. ; Das, Dipak K. / Cardioprotection by adaptation to ischaemia augments autophagy in association with BAG-1 protein. In: Journal of Cellular and Molecular Medicine. 2009 ; Vol. 13, No. 2. pp. 373-387.
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