Activation of Mitochondrial Large-Conductance Calcium-Activated K+ Channels via Protein Kinase A Mediates Desflurane-Induced Preconditioning

Redel, Andreas; Lange, Markus; Jazbutyte, Virginija; Lotz, Christopher; Smul, Thorsten M.; Roewer, Norbert; Kehl, Franz

doi:10.1213/ane.0b013e318160650f

Cited by 59 publications

(63 citation statements)

References 40 publications

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“…Concluding from other studies on the same experimental model, 21,23,28 we expected a myocardial IS of 50% (IS/AAR). Power analysis revealed a group size of n = 8 to detect a reduction in means of 15% with a power of 0.8 at a a-level of 0.05.…”

Section: Data Acquisition and Statistical Analysissupporting

confidence: 65%

Desflurane‐induced and ischaemic postconditioning against myocardial infarction are mediated by Pim‐1 kinase

Stumpner

Smul

Redel

et al. 2012

Acta Anaesthesiol Scand

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Background: Anaesthetic-induced (APOST) and ischaemic postconditioning (IPOST) against myocardial infarction are mediated via phosphatidylinositol-3-kinase/Akt. Pim-1 kinase is acting downstream of Akt and has recently been demonstrated to enhance cardiomyocyte survival. We tested the hypothesis that both APOST and IPOST are mediated by Pim-1 kinase. Methods: Pentobarbital-anaesthetized male C57BL/6 mice were subjected to 45-min coronary artery occlusion (CAO) and 3-h reperfusion. Animals received either no intervention, the Pim-1 kinase inhibitor II (10 mg/g intraperitoneally) or its vehicle dimethy sulfoxide (10 ml/g intraperitoneally). Three minutes prior to the end of CAO, 1.0 minimum alveolar concentration desflurane was administered for 18 min alone or in combination with Pim-1 kinase inhibitor II. IPOST was induced by three cycles of each 10-s ischaemia/reperfusion, and animals received either IPOST alone or in combination with Pim-1 kinase inhibitor II. Infarct size was determined with triphenyltetrazolium chloride and area at risk with Evans blue. Protein expression of Pim-1 kinase, Bad, phospho-Bad Ser112 and B-cell

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Section: Data Acquisition and Statistical Analysissupporting

confidence: 65%

Desflurane‐induced and ischaemic postconditioning against myocardial infarction are mediated by Pim‐1 kinase

Stumpner

Smul

Redel

et al. 2012

Acta Anaesthesiol Scand

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“…In fact, cytoprotection by mK Ca channel activation is supported by the findings that a activator (NS1619) and blockers (charybdotoxin, paxilline) of the Ca 2+ -activated K + channel in the cell membrane (K Ca + channel) were effective in manipulation of the mK Ca channel in mitochondria [74,75], that K Ca channel openers limited infarct size and that blockers of the K Ca channel (paxilline, iberiotoxin, charybdotoxin) or knockdown of the β1 subunit of the K Ca + channel inhibited infarct size-limiting effects of adrenomedulin [75], desflurane [76], sildenafil, [77] and IPC [78]. Furthermore, transient activation of the mK Ca channel by NS1619, like that of the mK ATP channel, has been shown to increase ROS production, leading to transmission of cytoprotective signaling [79,80].…”

Section: Cytoprotective K + Channels In Mitochondriamentioning

confidence: 99%

Mitochondria and GSK-3β in Cardioprotection Against Ischemia/Reperfusion Injury

Miura

Tanno

2010

Cardiovasc Drugs Ther

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The mitochondrion is a powerhouse of the cell, a platform of cell signaling and decision-maker of cell death, including death by ischemia/reperfusion. Ischemia shuts off ATP production by mitochondria, and cell viability is compromised by energy deficiency and build-up of cytotoxic metabolites during ischemia. Furthermore, the mitochondrial permeability transition pore (mPTP) is primed by ischemia to open upon reperfusion, leading to reperfusion-induced cell necrosis. mPTP opening can be suppressed by ischemic preconditioning (IPC) and other interventions that induce phosphorylation of GSK-3beta. Activation of the mitochondrial ATP-sensitive K(+) channel (mK(ATP) channel) is an important signaling step in a trigger phase of IPC, which ultimately enhances GSK-3beta phosphorylation upon reperfusion, and this channel functions as a mediator of cytoprotection as well. The mitochondrial Ca(2+)-activated K(+) channel appears to play roles similar to those of the mK(ATP) channel, though regulatory mechanisms of the channels are different. Phosphorylated GSK-3beta inhibits mPTP opening presumably by multiple mechanisms, including preservation of hexokinase II in mPTP complex, prevention of interaction of cyclophilin-D with adenine nucleotide translocase, inhibition of p53 activation and attenuation of ATP hydrolysis during ischemia. However, cytoprotective signaling pathways to GSK-3beta phosphorylation and other mPTP regulatory factors are modified by co-morbidities, including type 2 diabetes, and such modification makes the myocardium refractory to IPC and other cardioprotective agents. Regulatory mechanisms of mPTP, and their alterations by morbidities frequently associated with ischemic heart disease need to be further characterized for translation of mitochondrial and mPTP biology to the clinical arena.

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“…Modern volatile anaesthetics as elicitors of cardiac preconditioning have been effectively demonstrated in cell culture experiments [1,2] and animal models [3,4,5,6]. There is also supporting evidence from clinical studies that anaesthetic-induced preconditioning (APC) is protective in the clinical setting [7,8,9].…”

Section: Introductionmentioning

confidence: 99%

“…Subsequent molecular investigations of DES-PC were conducted with focus on specific targets known from IPC [2,3,4,5,11,12] but the overall picture of the underlying mechanisms is still lacking. A couple of studies even showed that the signalling pathways may differ from IPC [6,13].…”

Section: Introductionmentioning

confidence: 99%

In VivoDesflurane Preconditioning Evokes Dynamic Alterations of Metabolic Proteins in the Heart - Proteomic Insights Strengthen the Link between Bioenergetics and Cardioprotection

Dyballa-Rukes

Schuh

Vogt

et al. 2014

Cell Physiol Biochem

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Background: The cardioprotective effect of anaesthetic preconditioning as measured by reduction of ischaemia-reperfusion (I/R) injury is a well described phenomenon. However little is known about the impact on the myocardial proteome. We therefore investigated proteome dynamics at different experimental time points of a preconditioning protocol. Methods: Using an in vivo rat model of desflurane-induced preconditioning (DES-PC) cardiac tissue proteomes were analysed by a gel-based comparative approach. Treatment-dependent protein alterations were assessed by intra-group comparisons. Proteins were identified by mass-spectrometry. Results: A total of 40 protein spots were altered during the 30-minutes lasting preconditioning protocol. None of the proteins was differentially regulated consistently at all experimental time points. Interestingly, 1) the repeated administration of desflurane mostly accounted for proteome alterations during DES-PC, 2) the majority of altered protein species showed a decrease in abundance, 3) these changes primarily affected metabolic proteins involved in NADH/NAD⁺ redox balance, calcium homeostasis and acidosis and 4) protein alterations were not exclusively due to expression changes but also represented modifications of specific protein isoforms. Conclusion: DES-PC evokes dynamic alterations in the cardiac proteome which substantiate a tight regulation of bioenergetic proteins. Unique protein modifications may play a more important role in the preconditioning response.

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Activation of Mitochondrial Large-Conductance Calcium-Activated K+ Channels via Protein Kinase A Mediates Desflurane-Induced Preconditioning

Abstract: These data suggest that desflurane-induced APC is mediated in part by activation of mitochondrial large-conductance K(Ca) channels, and that activation of these channels by desflurane is mediated by PKA.

Cited by 59 publications

References 40 publications

Desflurane‐induced and ischaemic postconditioning against myocardial infarction are mediated by Pim‐1 kinase

Desflurane‐induced and ischaemic postconditioning against myocardial infarction are mediated by Pim‐1 kinase

Mitochondria and GSK-3β in Cardioprotection Against Ischemia/Reperfusion Injury

In VivoDesflurane Preconditioning Evokes Dynamic Alterations of Metabolic Proteins in the Heart - Proteomic Insights Strengthen the Link between Bioenergetics and Cardioprotection

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