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The SAFE pathway is involved in the postconditioning mechanism of oxytocin in isolated rat heart

Polshekan, M. and Khori, V. and Alizadeh, A.M. and Ghayour-Mobarhan, M. and Saeidi, M. and Jand, Y. and Rajaei, M. and Farnoosh, G. and Jamialahmadi, K. (2019) The SAFE pathway is involved in the postconditioning mechanism of oxytocin in isolated rat heart. Peptides, 111. pp. 142-151.

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Oxytocin (OT) has a postconditioning effect against the ischemia-reperfusion (I/R) injury. However, its precise cardioprotection mechanism at the early reperfusion phase remains under debate. Our previous study revealed that OT postconditioning (OTpost) is cardioprotective by activating the Reperfusion Injury Salvage Kinase (RISK) pathway. Therefore, the present study is aimed to determine the biological effects of OTpost via the OT receptor and the activation of the JAK/STAT3 signaling pathway, mitochondrial adenosine triphosphate-dependent potassium channel (mitoKATP), nitric oxide (NO) release, and its anti-apoptotic effects against I/R injury in an isolated rat heart model. Sixty-three rats were randomly allocated to one of nine groups. OT was perfused 40 min prior to the regional ischemia or 15 min at the early reperfusion phase. AG490 (a JAK/STAT3 inhibitor), 5HD (a mitoKATP blocker), atosiban (an OT receptor antagonist), L-NAME (a nonspecific nitric oxide synthase inhibitor) were applied either alone or in combination with OT during the pre-ischemia phase and/or in the early reperfusion phase. Myocardial infarct size, hemodynamic factor, ventricular arrhythmia, coronary flow, cardiac biochemical marker, and the apoptosis index were determined at the end of reperfusion. Oxytocin postconditioning reduced infarct size, lactate dehydrogenase activity, arrhythmia score, ventricular fibrillation, and apoptosis. Moreover, AG490, 5HD, atosiban, and L-NAME abrogated the cardioprotective effects of OT. Our results demonstrated that the cardioprotective effects of OT are mediated by NO release, and the activation of mitoKATP and the SAFE pathway through the JAK/STAT3 signaling cascade that finally lead to decrease in the apoptosis index during the early reperfusion phase. © 2018 Elsevier Inc.

Item Type: Article
Additional Information: cited By 4
Uncontrolled Keywords: adenosine triphosphate; atosiban; Janus kinase; lactate dehydrogenase; n benzyl 2 cyano 3 (3,4 dihydroxyphenyl)acrylamide; n(g) nitroarginine methyl ester; nitric oxide; oxytocin; STAT3 protein; alpha-cyano-(3,4-dihydroxy)-N-benzylcinnamide; argiprestocin; lactate dehydrogenase; n(g) nitroarginine methyl ester; nitric oxide; oxytocin; tyrphostin, animal experiment; animal model; animal tissue; apoptosis; Article; controlled study; drug mechanism; enzyme activation; enzyme activity; heart muscle ischemia; heart protection; ischemic postconditioning; isolated heart; JAK-STAT signaling; male; nonhuman; priority journal; rat; reperfusion injury; analogs and derivatives; animal; drug effect; heart; ischemic postconditioning; metabolism; myocardial ischemia reperfusion injury; physiology; procedures, Animals; Apoptosis; Heart; Ischemic Postconditioning; L-Lactate Dehydrogenase; Male; Myocardial Reperfusion Injury; NG-Nitroarginine Methyl Ester; Nitric Oxide; Oxytocin; Rats; Tyrphostins; Vasotocin
Subjects: سیستم غدد WK
سیستم قلب وعروق WG
QS آناتومی انسان
QU بیوشیمی
فارماکولوژی QV
> دانشکده داروسازی > فارماکولوژی QV

مقالات نمایه شده محققین دانشگاه در سایت ,Web of Science ,Scopus
Divisions: معاونت تحقیقات و فناوری
Depositing User: GOUMS
Date Deposited: 18 Dec 2019 11:46
Last Modified: 18 Dec 2019 11:46
URI: http://eprints.goums.ac.ir/id/eprint/10457

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