Adiponectin Protects Hypoxia/Reoxygenation-Induced Cardiomyocyte Injury by Suppressing Autophagy

Abstract

Adiponectin is a cytokine produced by adipocytes and acts as a potential cardioprotective agent and plays an important role in myocardial ischemia/reperfusion injury. In a myocardial hypoxia/reoxygenation model using neonatal rat ventricular myocytes, we investigated the contribution of adiponectin-mediated autophagy to its cardioprotective effects. Cardiomyocytes were exposed to hypoxia/reoxygenation pretreated with or without adiponectin in the presence of absence of rapamycin. Cell viability was analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method. Western blotting assay was used to determine the expression levels of microtubule-associated proteins 1A/1B light chain 3B (LC3B), adenosine monophosphate-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), p62/sequestosome 1, unc-51 like autophagy activating kinase 1 (ULK1), and Beclin-1. Autophagosome formation was detected by monodansylcadaverine staining. We found that hypoxia induced a time dependent decline in cardiomyocyte viability, and increase in autophagy and reoxygenation further augmented hypoxia-induced autophagy induction and consequently reduced cell viability. Adiponectin treatment alleviated hypoxia/reoxygenation-induced cellular damage and autophagy in cardiomyocytes. Adiponectin treatment also attenuated hypoxia/reoxygenation-promoted cardiomyocyte autophagy even in the presence of another autophagy stimulator rapamycin in part by inhibiting vacuolar hydron-adenosine triphosphatase. Additionally, autophagy suppression by adiponectin during hypoxia/reoxygenation was associated with the attenuated phosphorylation of AMPK and ULK1, augmented phosphorylation of mTOR, and the reduced protein expression levels of Beclin-1 in cardiomyocytes. Taken together, these results suggest that adiponectin protects ischemia/reperfusion-induced cardiomyocytes by suppressing autophagy in part through AMPK/mTOR/ULK1/Beclin-1 signaling pathway.

Vascular Endothelial Cell-Derived Exosomal Sphingosylphosphorylcholine Attenuates Myocardial Ischemia–Reperfusion Injury through NR4A2-Mediated Mitophagy

“…SPC (5 μM) was added at the beginning of reoxygenation [ 66 ]. Controls were incubated under normoxic conditions for 12 h [ 67 ].…”

The mysterious association between adiponectin and endometriosis

“…It must be acknowledged that the regulatory effect of adiponectin on autophagy is not unilateral, as others have shown that adiponectin inhibits autophagy and reduces angiogenesis in the choroidal retinal endothelial cell line RF/6A in monkeys through activation of the PI3K/AKT/mTOR pathway ( Li et al, 2019 ). Adiponectin can protect against hypoxia/reperfusion injury-induced cardiomyocyte damage by inhibiting autophagy as well, an effect that may be related to the inhibition of the AMPK/mTOR/UKL1/Beclin-1 pathway ( Guo et al, 2022 ).…”

Ginsenoside Rb2 Regulates Tissue Autophagy in the Ischemic Penumbra Area And Delays Bmsc Senescence by Improving The Ischemic-Hypoxic Microenvironment ​

“…To visualize and analyze the PPI network, Cytoscape 3.8.2 was used. The hub gene of PNS therapeutic autophagy was identi ed by scanning relevant literature (Guo et al, 2022;Shi et al, 2017) as BECN1, MTOR, MAP1LC3B, GATA4, and TNNT2, and the hub gene network in the PPI network was obtained using CytoHubba in Cytoscape. The hub gene network that was discovered included 159 targets and 4395 edges.…”