Role of Caveolin-3 and Glucose Transporter-4 in Isoflurane-induced Delayed Cardiac Protection

Murakami, Yasuo; Kawaraguchi, Yoshitaka; Horikawa, Yousuke T.; Niesman, Ingrid R.; Kidd, Michael W.; Chin-Lee, Blake; Head, Brian P.; Patel, Piyush M.; Roth, David M.; Patel, Hemal H.

doi:10.1097/aln.0b013e3181d3d624

Cited by 53 publications

(61 citation statements)

References 56 publications

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“…The declining I/R tolerance is not unexpected given the influences of caveolae and cholesterol on key determinants of stress resistance (8,18,31,32,44,(52)(53)(54)(55)(56)(57). For example, M␤CD consistently inhibits BK Ca channel function across different cell types, and the channel has been implicated in cytoprotection and I/R injury.…”

Section: Discussionmentioning

confidence: 99%

Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection

Hoe

Schilling

Tarbit

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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See Hoe LE, Schilling JM, Tarbit E, Kiessling CJ, Busija AR, Niesman IR, Du Toit E, Ashton KJ, Roth DM, Headrick JP, Patel HH, Peart JN. Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection. Am J Physiol Heart Circ Physiol 307: H895-H903, 2014. First published July 25, 2014; doi:10.1152/ajpheart.00081.2014.-Cholesterol-rich caveolar microdomains and associated caveolins influence sarcolemmal ion channel and receptor function and protective stress signaling. However, the importance of membrane cholesterol content to cardiovascular function and myocardial responses to ischemiareperfusion (I/R) and cardioprotective stimuli are unclear. We assessed the effects of graded cholesterol depletion with methyl-␤-cyclodextrin (M␤CD) and lifelong knockout (KO) or overexpression (OE) of caveolin-3 (Cav-3) on cardiac function, I/R tolerance, and opioid receptor (OR)-mediated protection. Langendorff-perfused hearts from young male C57Bl/6 mice were untreated or treated with 0.02-1.0 mM M␤CD for 25 min to deplete membrane cholesterol and disrupt caveolae. Hearts were subjected to 25-min ischemia/45-min reperfusion, and the cardioprotective effects of morphine applied either acutely or chronically [sustained ligand-activated preconditioning (SLP)] were assessed. M␤CD concentration dependently reduced normoxic contractile function and postischemic outcomes in association with graded (10 -30%) reductions in sarcolemmal cholesterol. Cardioprotection with acute morphine was abolished with Ն20 M M␤CD, whereas SLP was more robust and only inhibited with Ն200 M M␤CD. Deletion of Cav-3 also reduced, whereas Cav-3 OE improved, myocardial I/R tolerance. Protection via SLP remained equally effective in Cav-3 KO mice and was additive with innate protection arising with Cav-3 OE. These data reveal the membrane cholesterol dependence of normoxic myocardial and coronary function, I/R tolerance, and OR-mediated cardioprotection in murine hearts (all declining with cholesterol depletion). In contrast, baseline function appears insensitive to Cav-3, whereas cardiac I/R tolerance parallels Cav-3 expression. Novel SLP appears unique, being less sensitive to cholesterol depletion than acute OR protection and arising independently of Cav-3 expression.cardioprotection; caveolae; caveolin-3; cholesterol; contractility; ischemia-reperfusion; membrane microdomains; opioid receptors SARCOLEMMAL MICRODOMAINS are critical regulators of cellular function and signaling (34) and may be important in sex-, age-, and disease-dependent differences in cardiac and vascular function (3,10,11,14,24,49,62). Caveolae are lipid rich (i.e., cholesterol and glycosphingolipid) microdomains containing scaffolding proteins, caveolins, that present as distinct molecular platforms for the regulation of cytoprotective and other signaling (52). However, the importance of membrane cholesterol and microdomains to the maintenance of myocardial and coronary function as well as intrinsic responses to insult/stress a...

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Section: Discussionmentioning

confidence: 99%

Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection

Hoe

Schilling

Tarbit

et al. 2014

American Journal of Physiology-Heart and Circulatory Physiology

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“…Taken together, these observations support the growing body of data that led to the recognition of myocardial lipid rafts and their associated proteins as modulators of cardiac performance and as novel therapeutic targets [73][74][75].…”

Section: Molecular Basis Of Dilated Cardiomyopathy: Past and New Actorsmentioning

confidence: 53%

Idiopathic Dilated Cardiomyopathy: Molecular Basis and Distilling Complexity to Advance

Roura¹,

Gálvez‐Montón²,

Lupón³

et al. 2017

Cardiomyopathies - Types and Treatments

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Cardiomyopathies are heterogeneous diseases of the myocardium associated with abnormal findings of chamber size, wall thickness, and/or functional contractility. In particular, dilated cardiomyopathy (DCM) is mainly characterized by ventricular chamber enlargement with systolic dysfunction and normal left ventricular (LV) wall thickness. Although DCM is thought to be induced mainly by genetic or environmental factors, in the majority of cases, the cause is unknown. With an estimated prevalence of 1:2500 and an incidence of 1:18,000 per year in adults, DCM is the most frequent indication for heart transplantation, which represents an enormous cost burden on healthcare systems. These figures warrant greater accuracy in patient diagnosis and prognosis and further insight into the underlying basis of DCM. Here, we discuss past and recent findings on the molecular mechanisms involved in DCM. Dilated cardiomyopathy has been linked to the overactivation of extracellular signal-regulated kinase (ERK1/2), which in turn is related to activation of low-density lipoprotein receptorrelated protein-1 (LRP-1). Moreover, a redistribution of LRP-1 into cholesterol-enriched plasma membrane domains (lipid rafts) and alterations in cardiac DNA methylation have been reported in failing hearts. In conclusion, more comprehensive analyses of myocardial lipid rafts and epigenetic mechanisms may advance our understanding of DCM causes and progression. In turn, this understanding may promote the development of innovative treatments.

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“…CON control group, SEVO sevoflurane group. *Significantly (p \ 0.05) different from CON group after reperfusion, n = 4 per group mechanisms have been extensively studied such as K ATP channel, NF-jB, 12-lipoxygenase and so on [5][6][7], but very few studies have focused on the role of apoptosis in delayed APC. Studies demonstrated that APC with sevoflurane protects myocardium from I/R not only protects myocardial by reduced infarct size, but also improves cardiac functional recovery, decreases post-ischemic myocardial stunning and attenuates myocardial apoptosis [3,8,18,19].…”

Section: Discussionmentioning

confidence: 99%

“…Kehl et al [13] reported that, unlike ischemic preconditioning, isoflurane does not produce a second window of protection (SWOP) 24 h after administration in dogs. However, others have reported that isoflurane has delayed cardiac protective effects using in vivo mouse myocardial I/R model [6] and delayed APC with sevoflurane has a similar effect on myocardial protection [2][3][4].…”

Section: Introductionmentioning

confidence: 98%

“…Our previous studies have also demonstrated that the volatile anesthetic sevoflurane offers cardiac protection in both acute and delayed preconditioning against myocardial ischemia/reperfusion (I/R) injury [3][4][5]. Many mechanisms contribute to the protection such as the reactive oxygen species, mitochondrial ATP-sensitive potassium (mitoK ATP ) channels, nuclear factor-kappa B (NF-jB) and anti-apoptosis [6][7][8][9][10]. It has been reported that volatile anesthetic preconditioning (APC) can reduce apoptotic cells and apoptosis regulatory protein both in vivo and in vitro [11,12].…”

Section: Introductionmentioning

confidence: 99%

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The changes of technetium-99m-labeled annexin-V in delayed anesthetic preconditioning during myocardial ischemia/reperfusion

et al. 2013

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This study was designed to use real-time imaging to test the hypothesis that delayed cardiac protection induced by volatile anesthetics inhibits apoptosis. Rats were divided into two groups. One group was exposed to 120 min of 33 % O 2 [control group (CON group)] and the other group was exposed to 2.5 % sevoflurane in 33 % O 2 for 120 min [sevoflurane group (SEVO group)]. Both groups were allowed to return to their cages for 24 h. After 24 h recovery, all rats underwent 30 min myocardial ischemia by occluding coronary artery followed by 2 h of reperfusion. After reperfusion, technetium-99m-labeled annexin-V was administered intravenously to identify apoptosis. Left ventricular samples were obtained to measure infarct size and radionuclide imaging and caspase-3. Radionuclide imaging indicated that apoptosis was reduced in SEVO group (0.78 % ± 0.82) when compared with the CON group (1.15 % ± 0.61), and the infarct size was also decreased in the SEVO group (40 % ± 7). The transferase dUTP nick end labeling (TUNEL)-positive cardiomyocytes in the SEVO group (16 % ± 6) were significantly decreased in the peri-infarct zone when compared with the CON group (28 % ± 4). After reperfusion, caspase-3 expression was significantly blunted in the SEVO group than in CON group (50 % ± 11 vs. 68 % ± 10, p \ 0.05). This study used technetium-99m-labeled annexin-V of real-time imaging to detect cardiomyocyte apoptosis and the results were confirmed by the TUNEL assay and caspase-3 expression. We concluded that delayed volatile anesthetic preconditioning (APC) protects against I/R in vivo. The method of technetium-99m-labeled annexin-V of real-time imaging can be used to detect cardiomyocyte apoptosis in delayed APC during ischemia/reperfusion.

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Role of Caveolin-3 and Glucose Transporter-4 in Isoflurane-induced Delayed Cardiac Protection

Cited by 53 publications

References 56 publications

Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection

Sarcolemmal cholesterol and caveolin-3 dependence of cardiac function, ischemic tolerance, and opioidergic cardioprotection

Idiopathic Dilated Cardiomyopathy: Molecular Basis and Distilling Complexity to Advance

The changes of technetium-99m-labeled annexin-V in delayed anesthetic preconditioning during myocardial ischemia/reperfusion

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