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Pim-1 Kinase Regulating Dynamics Related Protein 1 Mediates Sevoflurane Postconditioning-induced Cardioprotection / 中华医学杂志(英文版)
Chinese Medical Journal ; (24): 309-317, 2017.
Article in English | WPRIM | ID: wpr-303155
ABSTRACT
<p><b>BACKGROUND</b>It is well documented that sevoflurane postconditioning (SP) has a significant myocardial protection effect. However, the mechanisms underlying SP are still unclear. In the present study, we investigated the hypothesis that the Pim-1 kinase played a key role in SP-induced cardioprotection by regulating dynamics-related protein 1 (Drp1).</p><p><b>METHODS</b>A Langendorff model was used in this study. Seventy-two rats were randomly assigned into six groups as follows CON group, ischemia reperfusion (I/R) group, SP group , SP+proto-oncogene serine/threonine-protein kinase 1 (Pim-1) inhibitor II group, SP+dimethylsufoxide group, and Pim-1 inhibitor II group (n = 12, each). Hemodynamic parameters and infarct size were measured to reflect the extent of myocardial I/R injury. The expressions of Pim-1, B-cell leukemia/lymphoma 2 (Bcl-2) and cytochrome C (Cyt C) in cytoplasm and mitochondria, the Drp1 in mitochondria, and the total Drp1 and p-Drp1ser637 were measured by Western blotting. In addition, transmission electron microscope was used to observe mitochondrial morphology. The experiment began in October 2014 and continued until July 2016.</p><p><b>RESULTS</b>SP improved myocardial I/R injury-induced hemodynamic parametric changes, cardiac function, and preserved mitochondrial phenotype and decreased myocardial infarct size (24.49 ± 1.72% in Sev group compared with 41.98 ± 4.37% in I/R group; P< 0.05). However, Pim-1 inhibitor II significantly (P < 0.05) abolished the protective effect of SP. Western blotting analysis demonstrated that, compared with I/R group, the expression of Pim-1 and Bcl-2 in cytoplasm and mitochondria as well as the total p-Drp1ser637 in Sev group (P < 0.05) were upregulated. Meanwhile, SP inhibited Drp1 compartmentalization to the mitochondria followed by a reduction in the release of Cyt C. Pretreatment with Pim-1 inhibitor II significantly (P < 0.05) abolished SP-induced Pim-1/p-Drp1ser637 signaling activation.</p><p><b>CONCLUSIONS</b>These findings suggested that SP could attenuate myocardial ischemia-reperfusion injury by increasing the expression of the Pim-1 kinase. Upregulation of Pim-1 might phosphorylate Drp1 and prevent extensive mitochondrial fission through Drp1 cytosolic sequestration.</p>
Subject(s)
Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Myocardial Reperfusion Injury / Rats, Sprague-Dawley / Dynamins / Therapeutic Uses / Proto-Oncogene Proteins c-pim-1 / Quinazolinones / Ischemic Postconditioning / Hemodynamics / Metabolism Limits: Animals Language: English Journal: Chinese Medical Journal Year: 2017 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Pharmacology / Myocardial Reperfusion Injury / Rats, Sprague-Dawley / Dynamins / Therapeutic Uses / Proto-Oncogene Proteins c-pim-1 / Quinazolinones / Ischemic Postconditioning / Hemodynamics / Metabolism Limits: Animals Language: English Journal: Chinese Medical Journal Year: 2017 Type: Article