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Adiponectin Facilitates Postconditioning Cardioprotection through Both AMPK-Dependent Nuclear and AMPK-Independent Mitochondrial STAT3 Activation.
- Source :
-
Oxidative medicine and cellular longevity [Oxid Med Cell Longev] 2020 Mar 04; Vol. 2020, pp. 4253457. Date of Electronic Publication: 2020 Mar 04 (Print Publication: 2020). - Publication Year :
- 2020
-
Abstract
- Myocardial 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.<br />Competing Interests: The authors confirm that there are no conflicts of interest.<br /> (Copyright © 2020 Qiqi Zhu et al.)
- Subjects :
- AMP-Activated Protein Kinases antagonists & inhibitors
Animals
Cell Hypoxia drug effects
Cell Nucleus drug effects
Enzyme Activation drug effects
Hemodynamics drug effects
Ischemic Postconditioning
Male
Mitochondria drug effects
Myocardium enzymology
Myocardium pathology
Myocytes, Cardiac drug effects
Myocytes, Cardiac metabolism
Myocytes, Cardiac pathology
Rats, Sprague-Dawley
Signal Transduction drug effects
AMP-Activated Protein Kinases metabolism
Adiponectin pharmacology
Cardiotonic Agents metabolism
Cell Nucleus metabolism
Mitochondria metabolism
STAT3 Transcription Factor metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1942-0994
- Volume :
- 2020
- Database :
- MEDLINE
- Journal :
- Oxidative medicine and cellular longevity
- Publication Type :
- Academic Journal
- Accession number :
- 32190173
- Full Text :
- https://doi.org/10.1155/2020/4253457