Role of Tyrosine Kinase in Desflurane-induced Preconditioning

Ebel, D.; Müllenheim, Jost; Südkamp, Hendrik; Bohlen, Thomas; Ferrari, Jan; Huhn, Ragnar; Preckel, Benedikt; Schlack, W.

doi:10.1097/00000542-200403000-00014

Cited by 11 publications

(7 citation statements)

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“…6 In contrast, activation of tyrosine kinase is required in IPC 29,30 but not necessarily in pharmacological preconditioning. 31 During the early phase of reperfusion, it is now well established that IPC activates the RISK pathway. 32,33 In addition, many pharmacological agents, such as adenosine agonists, bradykinin, atorvastatin, urocortin, insulin, and cardiotrophin-1, all protect the heart by activating the RISK pathway when given at the beginning of reperfusion.…”

Section: Discussionmentioning

confidence: 99%

Pharmacological Preconditioning With Tumor Necrosis Factor-α Activates Signal Transducer and Activator of Transcription-3 at Reperfusion Without Involving Classic Prosurvival Kinases (Akt and Extracellular Signal–Regulated Kinase)

et al. 2005

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Background-We previously reported that tumor necrosis-factor-␣ (TNF-␣) can mimic classic ischemic preconditioning (IPC) in a dose-and time-dependent manner. Because TNF-␣ activates the signal transducer and activator of transcription-3 (STAT-3), we hypothesized that TNF-␣-induced preconditioning requires phosphorylation of STAT-3 rather than involving the classic prosurvival kinases, Akt and extracellular signal-regulated kinase (Erk) 1/2, during early reperfusion. Methods and Results-Isolated, ischemic/reperfused rat hearts were preconditioned by either IPC or low-dose TNF-␣ (0.5 ng/mL). Western blot analysis confirmed that IPC phosphorylated Akt and Erk 1/2 after 5 minutes of reperfusion (Akt increased by 34Ϯ6% and Erk, by 105Ϯ28% versus control; PϽ0.01). Phosphatidylinositol 3-kinase/Akt inhibition (wortmannin) or mitogen-activated protein kinase-Erk 1/2 kinase inhibition (PD-98059) during early reperfusion abolished the infarct-sparing effect of IPC. In contrast, TNF-␣ preconditioning did not phosphorylate these kinases (Akt increased by 7Ϯ7% and Erk, by 17Ϯ14% versus control; PϭNS). Neither wortmannin nor PD-98059 inhibited TNF-␣-mediated cardioprotection. However, TNF-␣ and IPC both phosphorylated STAT-3 and the proapoptotic protein Bcl-2 antagonist of cell death (BAD) (STAT-3 increased by 58Ϯ17% with TNF-␣ or by 68Ϯ12% with IPC; BAD increased by 75Ϯ8% with TNF-␣ or by 205Ϯ20% with IPC; PϽ0.01 versus control), thereby activating the former and inactivating the latter. The STAT-3 inhibitor AG 490 abolished cardioprotection and BAD phosphorylation with both preconditioning stimuli. Conclusions-Activation of the classic prosurvival kinases (Akt and Erk 1/2) is not essential for TNF-␣-induced preconditioning in the early reperfusion phase. We show the existence of an alternative protective pathway that involves STAT-3 activation specifically at reperfusion in response to both TNF-␣ and classic IPC. This novel prosurvival pathway may have potential therapeutic significance. (Circulation. 2005;112:3911-3918.)

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Section: Discussionmentioning

confidence: 99%

Pharmacological Preconditioning With Tumor Necrosis Factor-α Activates Signal Transducer and Activator of Transcription-3 at Reperfusion Without Involving Classic Prosurvival Kinases (Akt and Extracellular Signal–Regulated Kinase)

et al. 2005

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“…There is also strong recent evidence demonstrating that desflurane confers a preconditioning‐like cardioprotection ( Toma et al , 2004 ; Tsai et al , 2004 ; Smul et al , 2006 ). This protection appears to involve both sarcolemmal and mitochondrial K ATP channels ( Toller et al , 2000 ) and mediated by NO ( Smul et al , 2006 ), but does not involve tyrosine kinase activation ( Ebel et al , 2004 ). Recently it has been suggested that signal transduction pathways associated with β1‐adrenergic receptor mediate anaesthetic preconditioning for desflurane and sevoflurane ( Lange et al , 2006 ).…”

Section: Anaesthetics As Cardioprotective Agentsmentioning

confidence: 99%

Inflammatory response and cardioprotection during open‐heart surgery: the importance of anaesthetics

Suleiman

Zacharowski

Angelini

2008

British J Pharmacology

137

108

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Open-heart surgery triggers an inflammatory response that is largely the result of surgical trauma, cardiopulmonary bypass, and organ reperfusion injury (e.g. heart). The heart sustains injury triggered by ischaemia and reperfusion and also as a result of the effects of systemic inflammatory mediators. In addition, the heart itself is a source of inflammatory mediators and reactive oxygen species that are likely to contribute to the impairment of cardiac pump function. Formulating strategies to protect the heart during open heart surgery by attenuating reperfusion injury and systemic inflammatory response is essential to reduce morbidity. Although many anaesthetic drugs have cardioprotective actions, the diversity of the proposed mechanisms for protection (e.g. attenuating Ca 2 þ overload, anti-inflammatory and antioxidant effects, pre-and post-conditioning-like protection) may have contributed to the slow adoption of anaesthetics as cardioprotective agents during open heart surgery. Clinical trials have suggested at least some cardioprotective effects of volatile anaesthetics. Whether these benefits are relevant in terms of morbidity and mortality is unclear and needs further investigation. This review describes the main mediators of myocardial injury during open heart surgery, explores available evidence of anaesthetics induced cardioprotection and addresses the efforts made to translate bench work into clinical practice.

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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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Role of Tyrosine Kinase in Desflurane-induced Preconditioning

Abstract: Desflurane-induced preconditioning does not depend on tyrosine kinase activation.

Cited by 11 publications

References 0 publications

Pharmacological Preconditioning With Tumor Necrosis Factor-α Activates Signal Transducer and Activator of Transcription-3 at Reperfusion Without Involving Classic Prosurvival Kinases (Akt and Extracellular Signal–Regulated Kinase)

Pharmacological Preconditioning With Tumor Necrosis Factor-α Activates Signal Transducer and Activator of Transcription-3 at Reperfusion Without Involving Classic Prosurvival Kinases (Akt and Extracellular Signal–Regulated Kinase)

Inflammatory response and cardioprotection during open‐heart surgery: the importance of anaesthetics

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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