Quantitative characterization of changes in the cardiac mitochondrial proteome during anesthetic preconditioning and ischemia

Bienengraeber, Martin; Pellitteri-Hahn, Molly C.; Hirata, Naoyuki; Baye, Tesfaye M.; Bošnjak, Željko J.; Olivier, Michael

doi:10.1152/physiolgenomics.00117.2012

Cited by 9 publications

(13 citation statements)

References 30 publications

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“…The partial inhibition of complex III is already discussed to account for the cardioprotective properties of volatile anesthetics [39]. A recent proteomics study also detected decreased levels of UQCRC1 in isoflurane-preconditioned heart [16]. In accordance to this we found UQCRC1 to be diminished especially in response to the washout phases during the preconditioning protocol.…”

Section: Discussionsupporting

confidence: 85%

“…For instance Xiao and co-workers demonstrated several mitochondrial protein expression changes of proteins related to ATP generation and transport in a setup analysing delayed sevoflurane-preconditioning [15]. Bienengraeber et al could show that isoflurane-induced preconditioning predominantly affected complexes of the electron transport chain in the cardiac mitochondrial proteome [16]. In addition, metabolomics studies strengthen the link between bioenergetic profiles and cardioprotection [40,44].…”

Section: Discussionmentioning

confidence: 99%

“…myocardial tissue specimens. Nevertheless, proteomics approaches investigating the effect of APC remain scarce, and the three conducted studies exclusively examined the mitochondrial proteome after single-cycle exposure of isoflurane or sevoflurane [14,15,16]. Whether other proteins like cytosolic ones were changed was not determined.…”

Section: Introductionmentioning

confidence: 99%

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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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Section: Discussionsupporting

confidence: 85%

Section: Discussionmentioning

confidence: 99%

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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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“…AGEs upregulated the ROS production, Cyt c release (He et al, 2011;Knels et al, 2008), and then promoted the activation of casapases and led to target cell apoptosis (Yoshimaru et al, 2008). Moreover, anesthetics also exert pressure on mitochondria and even promote mitochondrial dysfunction and lead to apoptotic cell death (Bienengraeber et al, 2013;Zhang et al, 2010). Our results in mitochondrial function analysis confirmed that AGEs and etomidate could synergistically induce oxidative stress.…”

Section: Discussionsupporting

confidence: 63%

Etomidate deteriorates the toxicity of advanced glycation end products to human endothelial Eahy926 cells

Wang

Jin

et al. 2014

J. Toxicol. Sci.

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-Patients with diabetes mellitus, particularly those with cardiovascular complications, have increased risk of mortality when subject to anesthetics and surgery, compared with non-diabetic patients. Anesthetics may exert pressure on the cardiovascular system of diabetic patients, directly or by aggravating pre-existing cardiovascular complications. Advanced glycation end products (AGEs) are extremely accumulated in diabetes mellitus, and are confirmed to play an important role in the pathogenesis of diabetic microvascular and macrovascular complications. The purpose of the present study was to investigate the regulatory role of etomidate, which is widely used as intravenous general anesthetics, on the viability and apoptosis of human endothelial Eahy926 cells, in the presence of AGEs. The results demonstrated that etomidate and Glu-BSA (one type of AGE) synergistically reduced the human endothelial Eahy926 cell viability and induced cell apoptosis. In addition, western blot assay of apoptosis-associated molecules indicated that both agents synergistically upregulated the cytochrome c release, activated the apoptosis executor, caspase 3, and promoted the poly-ADP-ribose polymerase (PARP) lysis. Further results confirmed that the two agents synergistically promoted oxidative stress by decreasing mitochondrial respiratory chain complex IV and mitochondrial membrane potential (MMP), while upregulating reactive oxygen species (ROS) and mitochondrial superoxide. In conclusion, the results presented in this study offer a novel insight into the mechanisms of endothelial cell apoptosis in response to etomidate in the presence of AGEs. These results suggest that oxidative stress has important role in the synergistic promotion of apoptosis by etomidate and AGEs in endothelial Eahy926 cells.

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“…The same protocol has been established in our previous studies and mirrors a clinically relevant dosage. 17,18 Control cells remained in the same incubator throughout the experiment. Isoflurane-exposed cells were removed from the sealed chamber and placed with control cells for 15 minutes to allow for washout of the volatile anesthetic before RNA isolation.…”

Section: Methodsmentioning

confidence: 99%

Up-regulation of MicroRNA-21 Mediates Isoflurane-induced Protection of Cardiomyocytes

et al. 2015

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Background Anesthetic cardioprotection reduces myocardial infarct size following ischemia-reperfusion injury. Currently, the role of microRNA in this process remains unknown. MicroRNAs are short, non-coding nucleotide sequences that negatively regulate gene expression through degradation or suppression of messenger RNA. In this study, we uncovered the functional role of microRNA-21 (miR-21) upregulation after anesthetic exposure. Methods MicroRNA and messenger RNA expression changes were analyzed by quantitative real-time polymerase chain reaction in cardiomyocytes after exposure to isoflurane. Lactate dehydrogenase release assay and propidium iodide staining were conducted after inhibition of miR-21. miR-21 target expression was analyzed by Western Blot. The functional role of miR-21 was confirmed in vivo in both wild type and miR-21 knockout mice. Results Isoflurane induces an acute upregulation of miR-21 in both in vivo and in vitro rat models (n = 6, 247.8 ± 27.5% and 258.5 ± 9.0%), which mediates protection to cardiomyocytes through downregulation of programmed cell death protein 4 (PDCD4) messenger RNA (n = 3, 82.0 ± 4.9% of control group). This protective effect was confirmed through knockdown of miR-21 and PDCD4 in vitro. Additionally, the protective effect of isoflurane was abolished in miR-21 knockout mice in vivo, with no significant decrease in infarct size compared to non-exposed controls (n = 8, 62.3 ± 4.6% and 56.2 ± 3.2%). Conclusions We demonstrate for the first time that isoflurane mediates protection of cardiomyocytes against oxidative stress via a miR-21/PDCD4 pathway. These results reveal a novel mechanism by which the damage done by ischemia-reperfusion injury may be decreased.

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Quantitative characterization of changes in the cardiac mitochondrial proteome during anesthetic preconditioning and ischemia

Abstract: Bienengraeber M, Pellitteri-Hahn M, Hirata N, Baye TM, Bosnjak ZJ, Olivier M. Quantitative characterization of changes in the cardiac mitochondrial proteome during anesthetic preconditioning and ischemia.

Cited by 9 publications

References 30 publications

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

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

Etomidate deteriorates the toxicity of advanced glycation end products to human endothelial Eahy926 cells

Up-regulation of MicroRNA-21 Mediates Isoflurane-induced Protection of Cardiomyocytes

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