Wang 2019 Life Sci

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Wang JW, Xue ZY, Wu AS (2019) Mechanistic insights into δ-opioid-induced cardioprotection: Involvement of caveolin translocation to the mitochondria. Life Sci 247:116942.

» PMID: 31715185

Wang JW, Xue ZY, Wu AS (2019) Life Sci

Abstract: The cardioprotective effects of preconditioning against ischemia-reperfusion (I/R) injury depend on the structural integrity of membrane caveolae and signaling through G protein-coupled receptors (GPCRs). However, the mechanisms underlying opioid preconditioning are not fully understood. Here, we examined whether caveolins transmitted opioid-GPCR signals to the mitochondria to mediate cardioprotection.

Mice were treated with pertussis toxin (PTX) or saline. Thirty-six hours later, mice from each group were randomly assigned to receive the δ-opioid receptor agonist SNC-121 or saline intraperitoneally 15 min before in vivo I/R. Infarct sizes in each group were compared, and immunoblot analysis was used to detect caveolin expression. The structures of caveolae and mitochondria were determined by electron microscopy (EM). The opening degree of the mitochondrial permeability transition pore (mPTP) was assessed by colorimetry, and mitochondrial respiratory function was assessed by Oxygraph-2k.

Treatment with an opioid receptor agonist reduced the myocardial infarct size after I/R injury, increased caveolin expression, decreased mitochondrial mPTP opening, and improved mitochondrial respiratory function. EM analysis revealed that opioids induced caveolae formation in myocytes and tended to promote translocation to mitochondria. However, these protective effects were blocked by PTX.

Opioid-induced preconditioning depended on Gi signaling, which promoted caveolin translocation to mitochondria, supported their functional integrity, and enhanced cardiac stress adaption. Verification of this pathway will establish new targets for opioid agents in the field of cardiac protection.

Copyright © 2019. Published by Elsevier Inc.

Keywords: Caveolin, G protein-coupled receptor, Ischemia reperfusion injury, Mitochondria, Opioid receptor Bioblast editor: Plangger M

Labels: MiParea: Respiration, Pharmacology;toxicology 

Stress:Ischemia-reperfusion  Organism: Mouse  Tissue;cell: Heart  Preparation: Isolated mitochondria 

Coupling state: LEAK, OXPHOS  Pathway: N, S  HRR: Oxygraph-2k 

Labels, 2019-11