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Article: Adiponectin Facilitates Postconditioning Cardioprotection Through Both AMPK-Dependent Nuclear and AMPK-Independent Mitochondrial STAT3 Activation

TitleAdiponectin Facilitates Postconditioning Cardioprotection Through Both AMPK-Dependent Nuclear and AMPK-Independent Mitochondrial STAT3 Activation
Authors
KeywordsMitochondria
AMP-activated protein kinase
Biological effects
Myocardial injury
Myocardial ischemia-reperfusion
Issue Date2020
PublisherHindawi Publishing Corporation. The Journal's web site is located at http://www.hindawi.com/journals/oximed/
Citation
Oxidative Medicine and Cellular Longevity, 2020, v. 2020, p. article no. 4253457 How to Cite?
AbstractMyocardial ischemic postconditioning- (IPo-) mediated cardioprotection against myocardial ischemia-reperfusion (IR) injury needs the activation of signal transducer and activator of transcription 3 (STAT3), which involves adiponectin (APN). APN confers its biological effects through AMP-activated protein kinase- (AMPK-) dependent and AMPK-independent pathways. However, the role of AMPK in APN-mediated STAT3 activation in IPo cardioprotection is unknown. We hypothesized that APN-mediated STAT3 activation in IPo is AMPK-independent and that APN through AMPK-dependent STAT3 activation facilitates IPo cardioprotection. Here, Sprague-Dawley rats were subjected to myocardial IR without or with IPo and/or APN. APN or IPo significantly improved postischemic cardiac function and reduced myocardial injury and oxidative stress, and their combination further attenuated postischemic myocardial injuries. APN or its combination with IPo but not IPo alone significantly increased AMPK activation and both nuclear and mitochondrial STAT3 activation, while IPo significantly enhanced mitochondrial but not nuclear STAT3 activation. In primarily isolated cardiomyocytes, recombined globular APN (gAd), hypoxic postconditioning (HPo), or their combination significantly attenuated hypoxia/reoxygenation-induced cell injury and increased nuclear and/or mitochondrial STAT3 activation. STAT3 inhibition had no impact on gAd or gAd in combination with HPo-induced AMPK activation but abolished their cellular protective effects. AMPK inhibition did not affect HPo cardioprotection but abolished gAd cardioprotection and disabled gAd to facilitate/enhance HPo cardioprotection and STAT3 activation. These results suggest that APN confers cardioprotection through AMPK-dependent and AMPK-independent STAT3 activation, while IPo confers cardioprotection through AMPK-independent mitochondrial STAT3 activation. Joint use of APN and IPo synergistically attenuated myocardial IR injury by activating STAT3 via distinct signaling pathways.
Persistent Identifierhttp://hdl.handle.net/10722/282505
ISSN
2019 Impact Factor: 5.076
2015 SCImago Journal Rankings: 1.503
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorZhu, Q-Q-
dc.contributor.authorLi, H-
dc.contributor.authorXie, X-
dc.contributor.authorKosuru, R-
dc.contributor.authorLi, S-
dc.contributor.authorLian, Q-Q-
dc.contributor.authorCheung, CW-
dc.contributor.authorIrwin, MG-
dc.contributor.authorGe, R-S-
dc.contributor.authorXia, Z-
dc.date.accessioned2020-05-15T05:28:59Z-
dc.date.available2020-05-15T05:28:59Z-
dc.date.issued2020-
dc.identifier.citationOxidative Medicine and Cellular Longevity, 2020, v. 2020, p. article no. 4253457-
dc.identifier.issn1942-0900-
dc.identifier.urihttp://hdl.handle.net/10722/282505-
dc.description.abstractMyocardial ischemic postconditioning- (IPo-) mediated cardioprotection against myocardial ischemia-reperfusion (IR) injury needs the activation of signal transducer and activator of transcription 3 (STAT3), which involves adiponectin (APN). APN confers its biological effects through AMP-activated protein kinase- (AMPK-) dependent and AMPK-independent pathways. However, the role of AMPK in APN-mediated STAT3 activation in IPo cardioprotection is unknown. We hypothesized that APN-mediated STAT3 activation in IPo is AMPK-independent and that APN through AMPK-dependent STAT3 activation facilitates IPo cardioprotection. Here, Sprague-Dawley rats were subjected to myocardial IR without or with IPo and/or APN. APN or IPo significantly improved postischemic cardiac function and reduced myocardial injury and oxidative stress, and their combination further attenuated postischemic myocardial injuries. APN or its combination with IPo but not IPo alone significantly increased AMPK activation and both nuclear and mitochondrial STAT3 activation, while IPo significantly enhanced mitochondrial but not nuclear STAT3 activation. In primarily isolated cardiomyocytes, recombined globular APN (gAd), hypoxic postconditioning (HPo), or their combination significantly attenuated hypoxia/reoxygenation-induced cell injury and increased nuclear and/or mitochondrial STAT3 activation. STAT3 inhibition had no impact on gAd or gAd in combination with HPo-induced AMPK activation but abolished their cellular protective effects. AMPK inhibition did not affect HPo cardioprotection but abolished gAd cardioprotection and disabled gAd to facilitate/enhance HPo cardioprotection and STAT3 activation. These results suggest that APN confers cardioprotection through AMPK-dependent and AMPK-independent STAT3 activation, while IPo confers cardioprotection through AMPK-independent mitochondrial STAT3 activation. Joint use of APN and IPo synergistically attenuated myocardial IR injury by activating STAT3 via distinct signaling pathways.-
dc.languageeng-
dc.publisherHindawi Publishing Corporation. The Journal's web site is located at http://www.hindawi.com/journals/oximed/-
dc.relation.ispartofOxidative Medicine and Cellular Longevity-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectMitochondria-
dc.subjectAMP-activated protein kinase-
dc.subjectBiological effects-
dc.subjectMyocardial injury-
dc.subjectMyocardial ischemia-reperfusion-
dc.titleAdiponectin Facilitates Postconditioning Cardioprotection Through Both AMPK-Dependent Nuclear and AMPK-Independent Mitochondrial STAT3 Activation-
dc.typeArticle-
dc.identifier.emailCheung, CW: cheucw@hku.hk-
dc.identifier.emailIrwin, MG: mgirwin@hku.hk-
dc.identifier.emailXia, Z: zyxia@hkucc.hku.hk-
dc.identifier.authorityCheung, CW=rp00244-
dc.identifier.authorityIrwin, MG=rp00390-
dc.identifier.authorityXia, Z=rp00532-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1155/2020/4253457-
dc.identifier.pmid32190173-
dc.identifier.pmcidPMC7073496-
dc.identifier.scopuseid_2-s2.0-85082059874-
dc.identifier.hkuros309944-
dc.identifier.volume2020-
dc.identifier.spagearticle no. 4253457-
dc.identifier.epagearticle no. 4253457-
dc.publisher.placeUnited States-

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