Co-ordinated autophagy with resveratrol and γ-tocotrienol confers synergetic cardioprotection

I. Lekli, Diptarka Ray, Subhendu Mukherjee, Narasimman Gurusamy, Md Kaimul Ahsan, B. Juhász, I. Bak, A. Tósaki, Mihaela Gherghiceanu, Lawrence M. Popescu, Dipak K. Das

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

This study compared two dietary phytochemicals, grape-derived resveratrol and palm oil-derived γ-tocotrienol, either alone or in combination, on the contribution of autophagy in cardioprotection during ischaemia and reperfusion. Sprague-Dawley rats weighing between 250 and 300 g were randomly assigned to one of the following groups: vehicle, ischaemia/reperfusion (I/R), resveratrol + I/R, γ-tocotrienol + I/R, resveratrol +γ-tocotrienol + I/R. For resveratrol treatments, the rats were gavaged with resveratrol (2.5 mg/kg) for 15 days while for γ-tocotrienol experiments the rats were gavaged with γ-tocotrienol (0.3 mg/kg) for 30 days. For the combined resveratrol +γ-tocotrienol experiments, the rats were gavaged with γ-tocotrienol for 15 days, and then gavaging continued with resveratrol along with γ-tocotrienol for a further period of 15 days. After 30 days, isolated perfused hearts were subjected to 30 min. of global ischaemia followed by 2 hrs of reperfusion. Our results showed for the first time that at least in part, the cardioprotection (evidenced from the ventricular performance, myocardial infarct size and cardiomyocyte apoptosis) with resveratrol and γ-toctrienol was achieved by their abilities to induce autophagy. Most importantly, resveratrol and γ-tocotrienol acted synergistically providing greater degree of cardioprotection simultaneously generating greater amount of survival signal through the activation of Akt-Bcl-2 survival pathway. Autophagy was accompanied by the activation of Beclin and LC3-II as well as mTOR signalling, which were inhibited by either 3-methyl adenine (3-MA) or Wortmannin. The autophagy was confirmed from the results of transmission electron microscopy and light microscopy as well as with confocal microscopy. It is tempting to speculate that during ischaemia and reperfusion autophagy along with enhanced survival signals helps to recover the cells from injury.

Original languageEnglish
Pages (from-to)2506-2518
Number of pages13
JournalJournal of Cellular and Molecular Medicine
Volume14
Issue number10
DOIs
Publication statusPublished - Oct 2010

Fingerprint

Tocotrienols
Autophagy
Reperfusion
Ischemia
resveratrol
Vitis
Phytochemicals
Adenine
Transmission Electron Microscopy
Cardiac Myocytes
Confocal Microscopy
Sprague Dawley Rats
Microscopy
Myocardial Infarction
Apoptosis
Light

Keywords

  • Autophagy
  • Resveratrol
  • Tocotrienol

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Medicine

Cite this

Co-ordinated autophagy with resveratrol and γ-tocotrienol confers synergetic cardioprotection. / Lekli, I.; Ray, Diptarka; Mukherjee, Subhendu; Gurusamy, Narasimman; Ahsan, Md Kaimul; Juhász, B.; Bak, I.; Tósaki, A.; Gherghiceanu, Mihaela; Popescu, Lawrence M.; Das, Dipak K.

In: Journal of Cellular and Molecular Medicine, Vol. 14, No. 10, 10.2010, p. 2506-2518.

Research output: Contribution to journalArticle

Lekli, I. ; Ray, Diptarka ; Mukherjee, Subhendu ; Gurusamy, Narasimman ; Ahsan, Md Kaimul ; Juhász, B. ; Bak, I. ; Tósaki, A. ; Gherghiceanu, Mihaela ; Popescu, Lawrence M. ; Das, Dipak K. / Co-ordinated autophagy with resveratrol and γ-tocotrienol confers synergetic cardioprotection. In: Journal of Cellular and Molecular Medicine. 2010 ; Vol. 14, No. 10. pp. 2506-2518.
@article{5ca911c0a36749daae2cf28a0d0e0257,
title = "Co-ordinated autophagy with resveratrol and γ-tocotrienol confers synergetic cardioprotection",
abstract = "This study compared two dietary phytochemicals, grape-derived resveratrol and palm oil-derived γ-tocotrienol, either alone or in combination, on the contribution of autophagy in cardioprotection during ischaemia and reperfusion. Sprague-Dawley rats weighing between 250 and 300 g were randomly assigned to one of the following groups: vehicle, ischaemia/reperfusion (I/R), resveratrol + I/R, γ-tocotrienol + I/R, resveratrol +γ-tocotrienol + I/R. For resveratrol treatments, the rats were gavaged with resveratrol (2.5 mg/kg) for 15 days while for γ-tocotrienol experiments the rats were gavaged with γ-tocotrienol (0.3 mg/kg) for 30 days. For the combined resveratrol +γ-tocotrienol experiments, the rats were gavaged with γ-tocotrienol for 15 days, and then gavaging continued with resveratrol along with γ-tocotrienol for a further period of 15 days. After 30 days, isolated perfused hearts were subjected to 30 min. of global ischaemia followed by 2 hrs of reperfusion. Our results showed for the first time that at least in part, the cardioprotection (evidenced from the ventricular performance, myocardial infarct size and cardiomyocyte apoptosis) with resveratrol and γ-toctrienol was achieved by their abilities to induce autophagy. Most importantly, resveratrol and γ-tocotrienol acted synergistically providing greater degree of cardioprotection simultaneously generating greater amount of survival signal through the activation of Akt-Bcl-2 survival pathway. Autophagy was accompanied by the activation of Beclin and LC3-II as well as mTOR signalling, which were inhibited by either 3-methyl adenine (3-MA) or Wortmannin. The autophagy was confirmed from the results of transmission electron microscopy and light microscopy as well as with confocal microscopy. It is tempting to speculate that during ischaemia and reperfusion autophagy along with enhanced survival signals helps to recover the cells from injury.",
keywords = "Autophagy, Resveratrol, Tocotrienol",
author = "I. Lekli and Diptarka Ray and Subhendu Mukherjee and Narasimman Gurusamy and Ahsan, {Md Kaimul} and B. Juh{\'a}sz and I. Bak and A. T{\'o}saki and Mihaela Gherghiceanu and Popescu, {Lawrence M.} and Das, {Dipak K.}",
year = "2010",
month = "10",
doi = "10.1111/j.1582-4934.2009.00921.x",
language = "English",
volume = "14",
pages = "2506--2518",
journal = "Journal of Cellular and Molecular Medicine",
issn = "1582-1838",
publisher = "Wiley-Blackwell",
number = "10",

}

TY - JOUR

T1 - Co-ordinated autophagy with resveratrol and γ-tocotrienol confers synergetic cardioprotection

AU - Lekli, I.

AU - Ray, Diptarka

AU - Mukherjee, Subhendu

AU - Gurusamy, Narasimman

AU - Ahsan, Md Kaimul

AU - Juhász, B.

AU - Bak, I.

AU - Tósaki, A.

AU - Gherghiceanu, Mihaela

AU - Popescu, Lawrence M.

AU - Das, Dipak K.

PY - 2010/10

Y1 - 2010/10

N2 - This study compared two dietary phytochemicals, grape-derived resveratrol and palm oil-derived γ-tocotrienol, either alone or in combination, on the contribution of autophagy in cardioprotection during ischaemia and reperfusion. Sprague-Dawley rats weighing between 250 and 300 g were randomly assigned to one of the following groups: vehicle, ischaemia/reperfusion (I/R), resveratrol + I/R, γ-tocotrienol + I/R, resveratrol +γ-tocotrienol + I/R. For resveratrol treatments, the rats were gavaged with resveratrol (2.5 mg/kg) for 15 days while for γ-tocotrienol experiments the rats were gavaged with γ-tocotrienol (0.3 mg/kg) for 30 days. For the combined resveratrol +γ-tocotrienol experiments, the rats were gavaged with γ-tocotrienol for 15 days, and then gavaging continued with resveratrol along with γ-tocotrienol for a further period of 15 days. After 30 days, isolated perfused hearts were subjected to 30 min. of global ischaemia followed by 2 hrs of reperfusion. Our results showed for the first time that at least in part, the cardioprotection (evidenced from the ventricular performance, myocardial infarct size and cardiomyocyte apoptosis) with resveratrol and γ-toctrienol was achieved by their abilities to induce autophagy. Most importantly, resveratrol and γ-tocotrienol acted synergistically providing greater degree of cardioprotection simultaneously generating greater amount of survival signal through the activation of Akt-Bcl-2 survival pathway. Autophagy was accompanied by the activation of Beclin and LC3-II as well as mTOR signalling, which were inhibited by either 3-methyl adenine (3-MA) or Wortmannin. The autophagy was confirmed from the results of transmission electron microscopy and light microscopy as well as with confocal microscopy. It is tempting to speculate that during ischaemia and reperfusion autophagy along with enhanced survival signals helps to recover the cells from injury.

AB - This study compared two dietary phytochemicals, grape-derived resveratrol and palm oil-derived γ-tocotrienol, either alone or in combination, on the contribution of autophagy in cardioprotection during ischaemia and reperfusion. Sprague-Dawley rats weighing between 250 and 300 g were randomly assigned to one of the following groups: vehicle, ischaemia/reperfusion (I/R), resveratrol + I/R, γ-tocotrienol + I/R, resveratrol +γ-tocotrienol + I/R. For resveratrol treatments, the rats were gavaged with resveratrol (2.5 mg/kg) for 15 days while for γ-tocotrienol experiments the rats were gavaged with γ-tocotrienol (0.3 mg/kg) for 30 days. For the combined resveratrol +γ-tocotrienol experiments, the rats were gavaged with γ-tocotrienol for 15 days, and then gavaging continued with resveratrol along with γ-tocotrienol for a further period of 15 days. After 30 days, isolated perfused hearts were subjected to 30 min. of global ischaemia followed by 2 hrs of reperfusion. Our results showed for the first time that at least in part, the cardioprotection (evidenced from the ventricular performance, myocardial infarct size and cardiomyocyte apoptosis) with resveratrol and γ-toctrienol was achieved by their abilities to induce autophagy. Most importantly, resveratrol and γ-tocotrienol acted synergistically providing greater degree of cardioprotection simultaneously generating greater amount of survival signal through the activation of Akt-Bcl-2 survival pathway. Autophagy was accompanied by the activation of Beclin and LC3-II as well as mTOR signalling, which were inhibited by either 3-methyl adenine (3-MA) or Wortmannin. The autophagy was confirmed from the results of transmission electron microscopy and light microscopy as well as with confocal microscopy. It is tempting to speculate that during ischaemia and reperfusion autophagy along with enhanced survival signals helps to recover the cells from injury.

KW - Autophagy

KW - Resveratrol

KW - Tocotrienol

UR - http://www.scopus.com/inward/record.url?scp=77958601200&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77958601200&partnerID=8YFLogxK

U2 - 10.1111/j.1582-4934.2009.00921.x

DO - 10.1111/j.1582-4934.2009.00921.x

M3 - Article

C2 - 19799646

AN - SCOPUS:77958601200

VL - 14

SP - 2506

EP - 2518

JO - Journal of Cellular and Molecular Medicine

JF - Journal of Cellular and Molecular Medicine

SN - 1582-1838

IS - 10

ER -