Reducing ischaemia/reperfusion injury through  -opioid-regulated intrinsic cardiac adrenergic cells: adrenopeptidergic co-signalling

Huang, Ming He; Nguyen, Vincent; Wu, Yuhong; Rastogi, Saurabh; Lui, Charles Y.; Birnbaum, Yochai; Wang, Hui Qun; Ware, David L.; Chauhan, Madhu; Garg, Nisha; Poh, Kian Keong; Ye, Lei; Omar, Abdul Razakjr; Tan, Huay Cheem; Uretsky, Barry F.; Fujise, Kenichi

doi:10.1093/cvr/cvp233

Cited by 36 publications

(43 citation statements)

References 36 publications

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“…Yao et al (33) reported that activation of the δ-opioid receptor reduces the apoptosis of myocardial cells through inhibition of the ERK and IP3 pathways. Furthermore, Huang et al (34) reported that activation of the δ-opioid receptor inhibits apoptosis by promoting CGRP expression in myocardial cells. A cell-type specific discrepancy between liver cells and myocardial cells may exist.…”

Section: Discussionmentioning

confidence: 99%

Activation of the δ-opioid receptor inhibits serum deprivation-induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway

Wang¹

2011

Int J Mol Med

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Abstract. Apoptosis of human liver cells is commonly found in liver diseases and liver surgery and directly affects their prognosis. Recent studies have found that δ-opioid receptors, abundant in the membranes of hepatic cells, participate in the oncogenesis and progression of liver tumors, viral hepatitis, liver cirrhosis and other diseases. The purpose of this study was to analyze the effect of the activation of the δ-opioid receptor on liver cell apoptosis and explore its relationship with PKC and the mitochondrial pathway. Hepatic cells were serum-deprived to induce apoptosis in vitro. During the period of apoptosis, mitochondrial membrane potential decreased, protein levels of cytosolic cytochrome c increased and the expression of Bcl-2 decreased, indicating that apoptosis was specifically induced by the mitochondrial pathway. Importantly, activation of δ-opioid receptors reversed the apoptotic state of hepatic cells. Following δ-opioid receptor activation, the mitochondrial membrane potential remained stable, and the expression of cytosolic cytochrome c and Bax decreased. These data suggest that δ-opioid receptor activation specifically inhibits the mitochondrial apoptotic pathway. In addition, activation of the δ-opioid receptor apparently increased the levels of PKC; blocking the PKC pathway led to increased apoptosis of liver cells, which was not affected by the activation of δ-opioid receptor. Blocking the PKC pathway led to increased apoptosis of liver cells, which was associated with δ-opioid receptor activation. Therefore, the PKC pathway is involved in the anti-apoptotic effects of the δ-opioid receptor on liver cells.

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Section: Discussionmentioning

confidence: 99%

Activation of the δ-opioid receptor inhibits serum deprivation-induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway

Wang¹

2011

Int J Mol Med

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“…Huang et al demonstrated that DPDPE markedly increased phosphorylated Akt levels in mouse cardiomyocytes. 40 In this study, we did not analyze the effect of PKC inhibition on Akt content as a result of DOR activation and thus the involvement of Akt signaling after DOR activation in MSCs remains unclear.…”

Section: Signaling Pathway For Msc Survival By Dor Activationmentioning

confidence: 96%

Delta-Opioid Receptor Activation Promotes Mesenchymal Stem Cell Survival via PKC/STAT3 Signaling Pathway

Higuchi

Masaaki

Zhu

et al. 2012

Circ J

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“…Among several potential mechanisms, Akt activation has been implicated as one of the key signaling pathways underling postconditioning mediated heart protection [1, 2], although species difference has been reported [3]. The mammalian heart possesses adrenopeptidergic neuroparacrine system consisting of intrinsic cardiac adrenergic (ICA) cells [4–6]. ICA cells synthesize and release epinephrine and calcitonin gene-related peptide (CGRP), stimulating myocardial β 2 -adrenoreceptor (β 2 -AR) and CGRP-receptors [5, 6], both of which being coupled to the adenylate cyclase-cAMP-dependent signaling pathway [7–9].…”

Section: Introductionmentioning

confidence: 99%

Heart Protection by Combination Therapy with Esmolol and Milrinone at Late-Ischemia and Early Reperfusion

Huang

Nguyen

et al. 2011

Cardiovasc Drugs Ther

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IntroductionThe present study determined whether late-ischemia/early reperfusion therapy with the β1-adrenergic receptor (AR) blocker esmolol and phosphodiesterase III inhibitor milrinone reduced left ventricular (LV) myocardial infarct size (IS).Methods and ResultsIn an ischemia/reperfusion rat model (30-min ischemia/4-hr reperfusion), esmolol, milrinone or esmolol + milrinone were intravenous (IV) infused over 10 min (from the last 5min of ischemia to the first 5min of reperfusion). LV-IS were 48.9 ± 8.9%, 41.5 ± 5.4%, 25.8 ± 7.7% and 16.8 ± 7.3% for saline, esmolol, milrinone, and esmolol + milrinone, respectively (n = 12/group). Esmolol + milrinone further reduced LV-IS compared with esmolol or milrinone alone (p < 0.05). LV-IS-reduction induced by esmolol + milrinone was eliminated in the presence of protein kinase A-(PKA)-inhibitor (Rp-cAMPS) or Akt-inhibitor (AKT 1/2 kinase inhibitor). In mixed rat ventricular cardiomyocyte cultures, intra-ischemic application of esmolol, milrinone or esmolol + milrinone reduced myocyte death rates by 5.5%, 13.3%, and 16.8%, respectively, compared with saline (p < 0.01). This cell protective effect by esmolol + milrinone was abrogated in the presence of PKA-inhibitor or Akt-inhibitor. Esmolol, milrinone or esmolol + milrinone increased myocardial PKA activity by 22%, 28% and 59%, respectively, compared with saline (n = 6, p < 0.01). No non-specific adverse effect of Rp-cAMPS on myocytes was identified in a purified myocyte preparation during hypoxia/re-oxygenation. Antiapoptotic pathways were assessed by measuring myocardial phosphorylated Akt (pAkt) levels combined with terminal dUTP nick-end labelling staining analysis. Ten minutes following infusion of esmolol, milrinone or esmolol + milrinone, there were 1.7-, 2.7-, and 6-fold increase in tissue pAkt levels, respectively. This esmolol + milrinone induced pAkt activation was abolished in the presence of PKA inhibitor. Esmolol, milrinone and esmolol + milrinone reduced myocyte apoptosis rates by 22%, 37% and 60%, respectively, compared with saline (p < 0.01).ConclusionsLate-ischemia/early reperfusion therapy with esmolol + milrinone additively reduces LV-IS associated with robust activation of myocardial PKA and subsequent Akt-antiapoptotic pathway.

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Reducing ischaemia/reperfusion injury through -opioid-regulated intrinsic cardiac adrenergic cells: adrenopeptidergic co-signalling

Abstract: ICA cells constitute a delta-opioid-regulated adrenopeptidergic paracrine system conferring robust cardioprotection through beta(2)-AR/CGRP-R co-signalling, resulting in the activation of an anti-apoptotic pathway during ischaemia/reperfusion.

Cited by 36 publications

References 36 publications

Activation of the δ-opioid receptor inhibits serum deprivation-induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway

Activation of the δ-opioid receptor inhibits serum deprivation-induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway

Delta-Opioid Receptor Activation Promotes Mesenchymal Stem Cell Survival via PKC/STAT3 Signaling Pathway

Heart Protection by Combination Therapy with Esmolol and Milrinone at Late-Ischemia and Early Reperfusion

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