title: Activation of the δ-opioid receptor inhibits serum deprivation-induced             apoptosis of human liver cells via the activation of PKC and the mitochondrial             pathway.
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.
authors.affiliation: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian 116027, PR China.
authors.forename: Bo
authors.initials: B
authors.lastname: Tang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Rui
authors.initials: R
authors.lastname: Liang
authors.forename: Peng
authors.initials: P
authors.lastname: Yuan
authors.forename: Jian
authors.initials: J
authors.lastname: Du
authors.forename: Hongxin
authors.initials: H
authors.lastname: Wang
authors.forename: Liming
authors.initials: L
authors.lastname: Wang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D045304:Cytochromes c / Q000235:genetics / Q000378:metabolism; D016308:Enkephalin, Leucine-2-Alanine / Q000494:pharmacology; D015870:Gene Expression; D022781:Hepatocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D011493:Protein Kinase C / Q000235:genetics / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017465:Receptors, Opioid, delta / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D044967:Serum / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013312:Stress, Physiological; D014407:Tumor Cells, Cultured; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D017465:Receptors, Opioid, delta; D051028:bcl-2-Associated X Protein; D009271:Naltrexone; D016308:Enkephalin, Leucine-2-Alanine; D045304:Cytochromes c; D011493:Protein Kinase C; C055382:naltrindole