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Lipid raft in cardiac health and disease.

Das M, Das DK - Curr Cardiol Rev (2009)

Bottom Line: Lipid rafts are sphingolipid and cholesterol rich micro-domains of the plasma membrane that coordinate and regulate varieties of signaling processes.Lipid rafts are also present in cardiac myocytes and are enriched in signaling molecules and ion channel regulatory proteins.At present, very little is known about the role of lipid rafts in cardiac function and dysfunction.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT 06030-110, USA.

ABSTRACT
Lipid rafts are sphingolipid and cholesterol rich micro-domains of the plasma membrane that coordinate and regulate varieties of signaling processes. Lipid rafts are also present in cardiac myocytes and are enriched in signaling molecules and ion channel regulatory proteins. Lipid rafts are receiving increasing attention as cellular organelles contributing to the pathogenesis of several structural and functional processes including cardiac hypertrophy and heart failure. At present, very little is known about the role of lipid rafts in cardiac function and dysfunction. This review will discuss the possible role of lipid rafts in cardiac health and disease.

No MeSH data available.


Related in: MedlinePlus

Proposed model of the role of lipid raft in the ischemic preconditioning of the heart. In I/R heart, anti-death signaling components (p38MAPKβ and ERK 1/2) remain bound (+) with caveolin, whereas there was reduced association (-) of death signaling components (p38MAPKα, JNK and caspase-3) with caveolin. These unbound death signaling components induces reperfusion injury in the heart by expressing (+) JNK, BAX and p53 in the myocardium. In PC heart, death signaling components remain bound (+) with caveolin, whereas there was reduced association (-) of anti-death signaling components with caveolin. These unbound anti-death/survival signaling components induced cardioprotection by expressing (+) AKT, Bcl-2 and Bcl-xl in the myocardium. When precondition was performed in presence of cyclodextrin, lipid raft disintegrator, there was no particular strong interaction of survival signaling components or death signaling components with caveolin. Due to the loss of fine control on the availability death and survival signals, heart can not generate survival signal (cardioprotection) in the PC heart in presence of lipid raft disintegrator, which was further confirmed by the expression (+) of JNK, BAX and p53 in myocardium of cyclodextrin treated heart. [I/R= ischemia reperfusion, PC= precondition]. [Reproduced from Fig. (8) of Cell Physiol Biochem 2008; 21: 325-334 with permission from Karger].
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Figure 1: Proposed model of the role of lipid raft in the ischemic preconditioning of the heart. In I/R heart, anti-death signaling components (p38MAPKβ and ERK 1/2) remain bound (+) with caveolin, whereas there was reduced association (-) of death signaling components (p38MAPKα, JNK and caspase-3) with caveolin. These unbound death signaling components induces reperfusion injury in the heart by expressing (+) JNK, BAX and p53 in the myocardium. In PC heart, death signaling components remain bound (+) with caveolin, whereas there was reduced association (-) of anti-death signaling components with caveolin. These unbound anti-death/survival signaling components induced cardioprotection by expressing (+) AKT, Bcl-2 and Bcl-xl in the myocardium. When precondition was performed in presence of cyclodextrin, lipid raft disintegrator, there was no particular strong interaction of survival signaling components or death signaling components with caveolin. Due to the loss of fine control on the availability death and survival signals, heart can not generate survival signal (cardioprotection) in the PC heart in presence of lipid raft disintegrator, which was further confirmed by the expression (+) of JNK, BAX and p53 in myocardium of cyclodextrin treated heart. [I/R= ischemia reperfusion, PC= precondition]. [Reproduced from Fig. (8) of Cell Physiol Biochem 2008; 21: 325-334 with permission from Karger].

Mentions: Ischemia/reperfusion injury activates p42/44 and p38MAPK, redistributes caveolin-3 and downregulates expression of caveolin-1 [80]. Disruption of caveolae using MβCD eliminates the ability of ischemia and pharmacological preconditioning to protect the cardiac myocyte from injury [81]. This is also supported by the decreased ability of Cav-1 KO mice to undergo pharmacological preconditioning [82]. Recent investigations also showed that pro-survival signaling components (e.g., ERK1/ 2, HO-1, eNOS and p38MAPKβ) translocate and/or interact with caveolin in ischemia/reperfusion heart and render the heart less abundance to pro-survival signal and induces myocardial injury. Similarly, in preconditioned heart death signaling components (e.g., p38MAPKα, JNK and Src) translocates and/or interact with caveolin in preconditioned heart and rendering the heart less exposed to death signaling components and more abundant to pro-survival signaling components [83, 84]. Although detail mechanism of action of caveolin is not very clear, but evidence indicates that proteasomes play a very important role in the interaction between caveolin and signaling components. However, overall observation indicates that caveolin plays a pivotal role in cardioprotection against ischemic injury (Fig. 1).


Lipid raft in cardiac health and disease.

Das M, Das DK - Curr Cardiol Rev (2009)

Proposed model of the role of lipid raft in the ischemic preconditioning of the heart. In I/R heart, anti-death signaling components (p38MAPKβ and ERK 1/2) remain bound (+) with caveolin, whereas there was reduced association (-) of death signaling components (p38MAPKα, JNK and caspase-3) with caveolin. These unbound death signaling components induces reperfusion injury in the heart by expressing (+) JNK, BAX and p53 in the myocardium. In PC heart, death signaling components remain bound (+) with caveolin, whereas there was reduced association (-) of anti-death signaling components with caveolin. These unbound anti-death/survival signaling components induced cardioprotection by expressing (+) AKT, Bcl-2 and Bcl-xl in the myocardium. When precondition was performed in presence of cyclodextrin, lipid raft disintegrator, there was no particular strong interaction of survival signaling components or death signaling components with caveolin. Due to the loss of fine control on the availability death and survival signals, heart can not generate survival signal (cardioprotection) in the PC heart in presence of lipid raft disintegrator, which was further confirmed by the expression (+) of JNK, BAX and p53 in myocardium of cyclodextrin treated heart. [I/R= ischemia reperfusion, PC= precondition]. [Reproduced from Fig. (8) of Cell Physiol Biochem 2008; 21: 325-334 with permission from Karger].
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2805812&req=5

Figure 1: Proposed model of the role of lipid raft in the ischemic preconditioning of the heart. In I/R heart, anti-death signaling components (p38MAPKβ and ERK 1/2) remain bound (+) with caveolin, whereas there was reduced association (-) of death signaling components (p38MAPKα, JNK and caspase-3) with caveolin. These unbound death signaling components induces reperfusion injury in the heart by expressing (+) JNK, BAX and p53 in the myocardium. In PC heart, death signaling components remain bound (+) with caveolin, whereas there was reduced association (-) of anti-death signaling components with caveolin. These unbound anti-death/survival signaling components induced cardioprotection by expressing (+) AKT, Bcl-2 and Bcl-xl in the myocardium. When precondition was performed in presence of cyclodextrin, lipid raft disintegrator, there was no particular strong interaction of survival signaling components or death signaling components with caveolin. Due to the loss of fine control on the availability death and survival signals, heart can not generate survival signal (cardioprotection) in the PC heart in presence of lipid raft disintegrator, which was further confirmed by the expression (+) of JNK, BAX and p53 in myocardium of cyclodextrin treated heart. [I/R= ischemia reperfusion, PC= precondition]. [Reproduced from Fig. (8) of Cell Physiol Biochem 2008; 21: 325-334 with permission from Karger].
Mentions: Ischemia/reperfusion injury activates p42/44 and p38MAPK, redistributes caveolin-3 and downregulates expression of caveolin-1 [80]. Disruption of caveolae using MβCD eliminates the ability of ischemia and pharmacological preconditioning to protect the cardiac myocyte from injury [81]. This is also supported by the decreased ability of Cav-1 KO mice to undergo pharmacological preconditioning [82]. Recent investigations also showed that pro-survival signaling components (e.g., ERK1/ 2, HO-1, eNOS and p38MAPKβ) translocate and/or interact with caveolin in ischemia/reperfusion heart and render the heart less abundance to pro-survival signal and induces myocardial injury. Similarly, in preconditioned heart death signaling components (e.g., p38MAPKα, JNK and Src) translocates and/or interact with caveolin in preconditioned heart and rendering the heart less exposed to death signaling components and more abundant to pro-survival signaling components [83, 84]. Although detail mechanism of action of caveolin is not very clear, but evidence indicates that proteasomes play a very important role in the interaction between caveolin and signaling components. However, overall observation indicates that caveolin plays a pivotal role in cardioprotection against ischemic injury (Fig. 1).

Bottom Line: Lipid rafts are sphingolipid and cholesterol rich micro-domains of the plasma membrane that coordinate and regulate varieties of signaling processes.Lipid rafts are also present in cardiac myocytes and are enriched in signaling molecules and ion channel regulatory proteins.At present, very little is known about the role of lipid rafts in cardiac function and dysfunction.

View Article: PubMed Central - PubMed

Affiliation: Cardiovascular Research Center, University of Connecticut School of Medicine, Farmington, CT 06030-110, USA.

ABSTRACT
Lipid rafts are sphingolipid and cholesterol rich micro-domains of the plasma membrane that coordinate and regulate varieties of signaling processes. Lipid rafts are also present in cardiac myocytes and are enriched in signaling molecules and ion channel regulatory proteins. Lipid rafts are receiving increasing attention as cellular organelles contributing to the pathogenesis of several structural and functional processes including cardiac hypertrophy and heart failure. At present, very little is known about the role of lipid rafts in cardiac function and dysfunction. This review will discuss the possible role of lipid rafts in cardiac health and disease.

No MeSH data available.


Related in: MedlinePlus