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

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.

Downregulation of Ezh2 expression by RNA interference induces cell cycle arrest in the G0/G1 phase and apoptosis in U87 human glioma cells

“…JC-1 staining and flow cytometry were used to detect changes in the mitochondrial membrane potential according to a previously published protocol (17). The fluorescence signals of the JC-1 monomer and polymer were detected by the FL1 and FL2 detectors, respectively.…”

Embelin-induced brain glioma cell apoptosis and cell cycle arrest via the mitochondrial pathway

“…Change in the mitochondrial membrane potential was analyzed with JC-1 staining and flow cytometry, as previously described (21). The fluorescence signal of JC-1 monomer and polymer were measured using FL1 and FL2 probes, respectively.…”

The Inflammatory Response to Cigarette Smoking Versus Inhaled Opium in the Liver: An Experimental Study

“…The findings about the triggering or inhibitory effects of opiates on inflammation systems are now conflicting. Although some studies emphasized anti-inflammatory effects of some opiates such as morphine [20], some others showed that the dual effect of opium on inflammation might be dependant to the type of the opioid receptors in the especial organs [21], that µ opioid receptor activation prevents acute hepatic inflammation and cell death and activation of the δ-opioid receptor inhibits serum deprivation induced apoptosis of human liver cells via the activation of PKC (protein kinase C) and the mitochondrial pathway [22,23], while some studies showed that administration of opioid receptors antagonists attenuate liver fibrosis [24]. Thus, impact of opium on liver inflammation systems should be assessed considering the types of activated opiate receptors in liver tissue.…”