Sevoflurane postconditioning protects isolated rat hearts against ischemia-reperfusion injury: the role of radical oxygen species, extracellular signal-related kinases 1/2 and mitochondrial permeability transition pore

Yao, Yun-Tai; Li, Lihuan; Chen, Lei; Wang, Weipeng; Li, Libing; Gao, Chang‐Qing

doi:10.1007/s11033-009-9755-4

Cited by 41 publications

(50 citation statements)

References 40 publications

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“…HPC appeared to modulate the endogenous ROS balance. The signaling role of ROS is also consistent with the significant blunting of the protective effects of postconditioning in isolated rat hearts and human myocardium by the ROS scavenger N-acetyl-L-cysteine or N-mercaptopropionylglycine [36, 37]. …”

Section: Discussionmentioning

confidence: 56%

Novel Functional Role of Heat Shock Protein 90 in Mitochondrial Connexin 43-Mediated Hypoxic Postconditioning

Huang

et al. 2017

Cell Physiol Biochem

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Background/Aims: Previous studies have shown that heat shock protein 90 (HSP90)-mediated mitochondrial import of connexin 43 (Cx43) is critical in preconditioning cardioprotection. The present study was designed to test whether postconditioning has the same effect as preconditioning in promoting Cx43 translocation to mitochondria and whether mitochondrial HSP90 modulates this effect. Methods: Cellular models of hypoxic postconditioning (HPC) from rat heart-derived H9c2 cells and neonatal rat cardiomyocytes were employed. The effects of HPC on cardiomyocytes apoptosis were examined by flow cytometry and Hoechst 33342 fluorescent staining. Reactive oxidative species (ROS) production was assessed with the peroxide-sensitive fluorescent probe 2′,7′-dichlorofluorescin in diacetate (DCFH-DA). The anti- and pro-apoptotic markers Bcl-2 and Bax, HSP90 and Cx43 protein levels were studied by Western blot analysis in total cell homogenate and sarcolemmal and mitochondrial fractions. The effects on HPC of the HSP90 inhibitor geldanamycin (GA), ROS scavengers superoxide dismutase (SOD) and catalase (CAT), and small interfering RNA (siRNA) targeting Cx43 and HSP90 were also investigated. Results: HPC significantly reduced hypoxia/reoxygenation (H/R)-induced cardiomyocyte apoptosis. These beneficial effects were accompanied by an increase in Bcl-2 levels and a decrease in Bax levels in both sarcolemmal and mitochondrial fractions. HPC with siRNA targeting Cx43 or the ROS scavengers SOD plus CAT significantly prevented ROS generation and HPC cardioprotection, but HPC with either SOD or CAT did not. These data strongly supported the involvement of Cx43 in HPC cardioprotection, likely via modulation of the ROS balance which plays a central role in HPC protection. Furthermore, HPC increased total and mitochondrial levels of HSP90 and the mitochondria-to-sarcolemma ratio of Cx43; blocking the function of HSP90 with the HSP90 inhibitor geldanamycin (GA) or siRNA targeting HSP90 prevented the protection of HPC and the HPC-induced association of Cx43, indicating that mitochondrial HSP90 was important for mitochondrial translocation of Cx43 during HPC. Conclusion: Mitochondrial HSP90 played a central role in HPC cardioprotection, and its activity was linked to the mitochondrial targeting of Cx43, the activation of which triggered ROS signaling and the subsequent reduction of redox stress. Consequently, its target gene, Bcl-2, was upregulated, and proapoptotic Bax was inhibited in the sarcolemma and mitochondria, ultimately attenuating H/R-induced cardiomyocyte apoptosis. These data reveal a novel mechanism of HPC protection.

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Section: Discussionmentioning

confidence: 56%

Novel Functional Role of Heat Shock Protein 90 in Mitochondrial Connexin 43-Mediated Hypoxic Postconditioning

Huang

et al. 2017

Cell Physiol Biochem

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“…In the present study, we chose 3% sevoflurane to post-condition the isolated rat hearts in a Langendorff perfusion system [28] . Intracellular mitogenactivated protein kinases (MAPKs) signaling cascades play a key role in the pathogenesis of cardiac and vascular disease.…”

Section: Discussionmentioning

confidence: 99%

Sevoflurane post-conditioning protects isolated rat hearts against ischemia-reperfusion injury via activation of the ERK1/2 pathway

et al. 2014

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Aim: To investigate the role of extracellular signal-regulated kinases (ERKs) in sevoflurane post-conditioning induced cardioprotection in vitro. Methods: Isolated rat hearts were subjected to 30 min ischemia followed by 120 min reperfusion (I/R). Sevoflurane post-conditioning was carried out by administration of O 2 -enriched gas mixture with 3% sevoflurane (SEVO) for 15 min from the onset of reperfusion. Cardiac functions, myocardial infarct size, myocardial ATP and NAD + contents, mitochondrial ultrastructure, and anti-apototic and antioncosis protein levels were measured. Results: Sevoflurane post-conditioning significantly improved the heart function, decreased infarct size and mitochondria damage, and increased myocardial ATP and NAD + content in the I/R hearts. Furthermore, sevoflurane post-conditioning significantly increased the levels of p-ERK and p-p70S6K, decreased the levels of porimin, caspase-8, cleaved caspase-3, and cytosolic cytochrome c in the I/R hearts. Co-administration of the ERK1/2 inhibitor PD98059 (20 μmol/L) abolished the sevoflurane-induced protective effects against myocardial I/R. Conclusion: Sevoflurane post-conditioning protects isolated rat hearts against myocardial I/R injury and inhibits cell oncosis and apoptosis via activation of the ERK1/2 pathway.

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“…Sevoflurane postconditioning has been reported to reduce myocardial infarct size and ameliorate cardiac functions in I/R rat hearts (Siegmund et al, 1997;Chen et al, 2008;Inamura et al, 2010). Some studies agreed that 3% sevoflurane postconditioning for 15 min conferred significant cardioprotection in isolated I/R rat hearts (He et al, 2008;Yao et al, 2010b), but our recent study found that 2.5% sevoflurane (1 MAC) postconditioning for 10 min was sufficient to improve myocardial function and reduce infarct size after global I/R in isolated rat hearts (Yu et al, 2010).…”

Section: Cardioprotection Effect Of Sevoflurane Postconditioningmentioning

confidence: 86%

“…A meta-analysis showed that sevoflurane reduces the rate of myocardial infarct size and mortality in patients undergoing cardiac surgery, though the underlying mechanism remains unclear (Landoni et al, 2007). Several recent studies have confirmed that sevoflurane postconditioning spares myocardial infarct size and improves contractile functions in I/R animals (Inamura et al, 2010;Yao et al, 2010b;Yu et al, 2010;Zheng et al, 2011). It is widely accepted that activating the phosphatidylinositol-3-kinase (PI3K)/Akt pathway is pivotal to cardioprotection by sevoflurane postconditioning against I/R injury (Yao et al, 2010a;Yu et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

“…The protection of rat hearts by sevoflurane postconditioning was achieved within the first few minutes of reperfusion (Obal et al, 2003;Inamura et al, 2010). Longer administration (more than two minutes) of sevoflurane had no extra cardioprotective effects (Obal et al, 2003), although it was reported to work after 15 min in some cases (He et al, 2008;Yao et al, 2010b). It seems that sevoflurane postconditioning needs time to activate downstream effectors, even though the exact duration of postconditioning and, especially, the underlying mechanisms remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Activation of Akt and cardioprotection against reperfusion injury are maximal with only five minutes of sevoflurane postconditioning in isolated rat hearts

Yao

Zhu

Zhang

et al. 2013

J. Zhejiang Univ. Sci. B

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It had been proved that administration of sevoflurane for the first two minutes of reperfusion effectively protects the heart against reperfusion injury in rats in vivo. Our aim was to investigate the duration of effective sevoflurane administration and its underlying mechanism in isolated rat hearts exposed to global ischemia/reperfusion (I/R) injury. Adult male Sprague-Dawley rats were randomly divided into six groups (n=12): a sham-operation group, an I/R group, and four sevoflurane postconditioning groups (S2, S5, S10, and S15). In the S2, S5, S10, and S15 groups, the duration times of sevoflurane administration were 2, 5, 10, and 15 min after the onset of reperfusion, respectively. The isolated rat hearts were mounted on the Langendorff system, and after a period of equilibrium were subjected to 40 min global ischemia and 120 min reperfusion. Left ventricular (LV) hemodynamic parameters were monitored throughout each experiment and the data at 30 min of equilibrium and 30, 60, 90, and 120 min of reperfusion were analyzed. Myocardial infarct size at the end of reperfusion (n=7 in each group) and the expression of myocardial phosphorylated Akt (p-Akt) after 15-min reperfusion were determined in a duplicate set of six groups of rat hearts (n=5 in each group). Compared with the I/R group, the S5, S10, and S15 groups had significantly improved left ventricular end-diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), and the maximal rate of rise or fall of the LV pressure (±dP/dt max ), and decreased myocardial infarct size (P<0.05), but not the S2 group. After 15 min of reperfusion, the expression of p-Akt was markedly up-regulated in the S5, S10, and S15 groups compared with that in the I/R group (P<0.05), but not in the S2 group. Sevoflurane postconditioning for 5 min was sufficient to activate Akt and exert maximal cardioprotection against I/R injury in isolated rat hearts.

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Sevoflurane postconditioning protects isolated rat hearts against ischemia-reperfusion injury: the role of radical oxygen species, extracellular signal-related kinases 1/2 and mitochondrial permeability transition pore

Cited by 41 publications

References 40 publications

Novel Functional Role of Heat Shock Protein 90 in Mitochondrial Connexin 43-Mediated Hypoxic Postconditioning

Novel Functional Role of Heat Shock Protein 90 in Mitochondrial Connexin 43-Mediated Hypoxic Postconditioning

Sevoflurane post-conditioning protects isolated rat hearts against ischemia-reperfusion injury via activation of the ERK1/2 pathway

Activation of Akt and cardioprotection against reperfusion injury are maximal with only five minutes of sevoflurane postconditioning in isolated rat hearts

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