Essential role of lipid raft in ischemic preconditioning

Manika Das, Mihaela Gherghiceanu, I. Lekli, Subhendu Mukherjee, Lawrence M. Popescu, Dipak K. Das

Research output: Article

30 Citations (Scopus)

Abstract

Lipid rafts represent a subcompartment of the plasma membrane that coordinate and regulate varieties of signaling processes while caveolins are the integral membrane protein of the lipid raft. To study the role of lipid raft in ischemic preconditioning (PC) of the heart, rat hearts were perfused by working mode and then preconditioned in absence or presence of a lipid raft disintegrator, Methyl-β-cyclodextrin. As expected, precondition made the heart resistant to ischemia reperfusion (I/R) injury as evident by improved ventricular performance, reduced myocardial infract size and cardiomyocyte apoptosis. Cyclodextrin abolished the cardioprotection. Transmission Electron Microscopy revealed severe degeneration, swelling of mitochondria, chromatin condensation and myofibril disarray in cyclodextrin treated PC heart similar to I/R heart. In the PC hearts, there was an increased association of the proapoptotic p38MAPKα with caveolin-1 while there was a reduced association of anti-apoptotic p38MAPKβ with caveolin-3 indicating that reduced amount of p38MAPKα and increased amount of p38MAPKβ were available to the adapted hearts thereby generating a survival signal. In contrast, there was very weak caveolin-MAP kinase interaction in cyclodextrin treated heart. Myocardial damage was further confirmed by reduced or no expression of anti-apoptotic phospho-AKT, Bcl2, Bcl-xl and increased expression of pro-apoptotic JNK, BAX, and p53 in methyl-β-cyclodextrin (lipid raft disintegrator) treated heart. These results indicate that lipid raft play a pivotal role in the generation of survival signal in PC or adapted heart and disintegration of lipid raft completely abolish cardioprotection.

Original languageEnglish
Pages (from-to)325-334
Number of pages10
JournalCellular Physiology and Biochemistry
Volume21
Issue number4
DOIs
Publication statusPublished - 2008

Fingerprint

Ischemic Preconditioning
Lipids
Cyclodextrins
Caveolins
Caveolin 3
Caveolin 1
Myofibrils
Membrane Lipids
Reperfusion Injury
Transmission Electron Microscopy
Cardiac Myocytes
Chromatin
Reperfusion
Mitochondria
Membrane Proteins
Phosphotransferases
Ischemia
Cell Membrane
Apoptosis

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

Das, M., Gherghiceanu, M., Lekli, I., Mukherjee, S., Popescu, L. M., & Das, D. K. (2008). Essential role of lipid raft in ischemic preconditioning. Cellular Physiology and Biochemistry, 21(4), 325-334. https://doi.org/10.1159/000129391

Essential role of lipid raft in ischemic preconditioning. / Das, Manika; Gherghiceanu, Mihaela; Lekli, I.; Mukherjee, Subhendu; Popescu, Lawrence M.; Das, Dipak K.

In: Cellular Physiology and Biochemistry, Vol. 21, No. 4, 2008, p. 325-334.

Research output: Article

Das, M, Gherghiceanu, M, Lekli, I, Mukherjee, S, Popescu, LM & Das, DK 2008, 'Essential role of lipid raft in ischemic preconditioning', Cellular Physiology and Biochemistry, vol. 21, no. 4, pp. 325-334. https://doi.org/10.1159/000129391
Das, Manika ; Gherghiceanu, Mihaela ; Lekli, I. ; Mukherjee, Subhendu ; Popescu, Lawrence M. ; Das, Dipak K. / Essential role of lipid raft in ischemic preconditioning. In: Cellular Physiology and Biochemistry. 2008 ; Vol. 21, No. 4. pp. 325-334.
@article{25f5df35f8cd4d5ca3d19f301bcc405d,
title = "Essential role of lipid raft in ischemic preconditioning",
abstract = "Lipid rafts represent a subcompartment of the plasma membrane that coordinate and regulate varieties of signaling processes while caveolins are the integral membrane protein of the lipid raft. To study the role of lipid raft in ischemic preconditioning (PC) of the heart, rat hearts were perfused by working mode and then preconditioned in absence or presence of a lipid raft disintegrator, Methyl-β-cyclodextrin. As expected, precondition made the heart resistant to ischemia reperfusion (I/R) injury as evident by improved ventricular performance, reduced myocardial infract size and cardiomyocyte apoptosis. Cyclodextrin abolished the cardioprotection. Transmission Electron Microscopy revealed severe degeneration, swelling of mitochondria, chromatin condensation and myofibril disarray in cyclodextrin treated PC heart similar to I/R heart. In the PC hearts, there was an increased association of the proapoptotic p38MAPKα with caveolin-1 while there was a reduced association of anti-apoptotic p38MAPKβ with caveolin-3 indicating that reduced amount of p38MAPKα and increased amount of p38MAPKβ were available to the adapted hearts thereby generating a survival signal. In contrast, there was very weak caveolin-MAP kinase interaction in cyclodextrin treated heart. Myocardial damage was further confirmed by reduced or no expression of anti-apoptotic phospho-AKT, Bcl2, Bcl-xl and increased expression of pro-apoptotic JNK, BAX, and p53 in methyl-β-cyclodextrin (lipid raft disintegrator) treated heart. These results indicate that lipid raft play a pivotal role in the generation of survival signal in PC or adapted heart and disintegration of lipid raft completely abolish cardioprotection.",
keywords = "Heart, Ischemia, Lipid raft, Precondition, Signal transduction",
author = "Manika Das and Mihaela Gherghiceanu and I. Lekli and Subhendu Mukherjee and Popescu, {Lawrence M.} and Das, {Dipak K.}",
year = "2008",
doi = "10.1159/000129391",
language = "English",
volume = "21",
pages = "325--334",
journal = "Cellular Physiology and Biochemistry",
issn = "1015-8987",
publisher = "S. Karger AG",
number = "4",

}

TY - JOUR

T1 - Essential role of lipid raft in ischemic preconditioning

AU - Das, Manika

AU - Gherghiceanu, Mihaela

AU - Lekli, I.

AU - Mukherjee, Subhendu

AU - Popescu, Lawrence M.

AU - Das, Dipak K.

PY - 2008

Y1 - 2008

N2 - Lipid rafts represent a subcompartment of the plasma membrane that coordinate and regulate varieties of signaling processes while caveolins are the integral membrane protein of the lipid raft. To study the role of lipid raft in ischemic preconditioning (PC) of the heart, rat hearts were perfused by working mode and then preconditioned in absence or presence of a lipid raft disintegrator, Methyl-β-cyclodextrin. As expected, precondition made the heart resistant to ischemia reperfusion (I/R) injury as evident by improved ventricular performance, reduced myocardial infract size and cardiomyocyte apoptosis. Cyclodextrin abolished the cardioprotection. Transmission Electron Microscopy revealed severe degeneration, swelling of mitochondria, chromatin condensation and myofibril disarray in cyclodextrin treated PC heart similar to I/R heart. In the PC hearts, there was an increased association of the proapoptotic p38MAPKα with caveolin-1 while there was a reduced association of anti-apoptotic p38MAPKβ with caveolin-3 indicating that reduced amount of p38MAPKα and increased amount of p38MAPKβ were available to the adapted hearts thereby generating a survival signal. In contrast, there was very weak caveolin-MAP kinase interaction in cyclodextrin treated heart. Myocardial damage was further confirmed by reduced or no expression of anti-apoptotic phospho-AKT, Bcl2, Bcl-xl and increased expression of pro-apoptotic JNK, BAX, and p53 in methyl-β-cyclodextrin (lipid raft disintegrator) treated heart. These results indicate that lipid raft play a pivotal role in the generation of survival signal in PC or adapted heart and disintegration of lipid raft completely abolish cardioprotection.

AB - Lipid rafts represent a subcompartment of the plasma membrane that coordinate and regulate varieties of signaling processes while caveolins are the integral membrane protein of the lipid raft. To study the role of lipid raft in ischemic preconditioning (PC) of the heart, rat hearts were perfused by working mode and then preconditioned in absence or presence of a lipid raft disintegrator, Methyl-β-cyclodextrin. As expected, precondition made the heart resistant to ischemia reperfusion (I/R) injury as evident by improved ventricular performance, reduced myocardial infract size and cardiomyocyte apoptosis. Cyclodextrin abolished the cardioprotection. Transmission Electron Microscopy revealed severe degeneration, swelling of mitochondria, chromatin condensation and myofibril disarray in cyclodextrin treated PC heart similar to I/R heart. In the PC hearts, there was an increased association of the proapoptotic p38MAPKα with caveolin-1 while there was a reduced association of anti-apoptotic p38MAPKβ with caveolin-3 indicating that reduced amount of p38MAPKα and increased amount of p38MAPKβ were available to the adapted hearts thereby generating a survival signal. In contrast, there was very weak caveolin-MAP kinase interaction in cyclodextrin treated heart. Myocardial damage was further confirmed by reduced or no expression of anti-apoptotic phospho-AKT, Bcl2, Bcl-xl and increased expression of pro-apoptotic JNK, BAX, and p53 in methyl-β-cyclodextrin (lipid raft disintegrator) treated heart. These results indicate that lipid raft play a pivotal role in the generation of survival signal in PC or adapted heart and disintegration of lipid raft completely abolish cardioprotection.

KW - Heart

KW - Ischemia

KW - Lipid raft

KW - Precondition

KW - Signal transduction

UR - http://www.scopus.com/inward/record.url?scp=42549124081&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=42549124081&partnerID=8YFLogxK

U2 - 10.1159/000129391

DO - 10.1159/000129391

M3 - Article

C2 - 18441521

AN - SCOPUS:42549124081

VL - 21

SP - 325

EP - 334

JO - Cellular Physiology and Biochemistry

JF - Cellular Physiology and Biochemistry

SN - 1015-8987

IS - 4

ER -