Human hepatic met-enkephalin and delta opioid receptor-1 immunoreactivities in viral and autoimmune hepatitis

Boyella, Vijaya; Nicastri, Anthony D.; Bergasa, Nora V.

doi:10.1016/s1665-2681(19)31851-4

Cited by 17 publications

(8 citation statements)

References 15 publications

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“…The met-enkephalin concentration is high in the liver of HCV patients and is a useful marker of hepatocellular damage in chronic HCV (Ciesla et al, 2006 ). Met-enkephalin activates MORs and DORs which enhance replication of HCV in hepatic cells (Bergasa and Boyella, 2008 ), particularly in the liver of HCV patients (Boyella et al, 2008 ), and also interferes with the anti-viral effect of type I interferon (Floreani et al, 2012 ). The low efficiency of interferon therapy for HCV treatment in some patients could be explained by the effects of hepatic met-enkephalins (Bergasa and Boyella, 2008 ; Boyella et al, 2008 ).…”

Section: Opioids and Viral Infectionmentioning

confidence: 99%

Opioids and Viral Infections: A Double-Edged Sword

et al. 2016

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Opioids and their receptors have received remarkable attention because they have the ability to alter immune function, which affects disease progression. In vitro and in vivo findings as well as observations in humans indicate that opioids and their receptors positively or negatively affect viral replication and virus-mediated pathology. The present study reviews recent insights in the role of opioids and their receptors in viral infections and discusses possible therapeutic opportunities. This review supports the emerging concept that opioids and their receptors have both favorable and unfavorable effects on viral disease, depending on the type of virus. Targeting of the opioid system is a potential option for developing effective therapies; however caution is required in relation to the beneficial functions of opioid systems.

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Section: Opioids and Viral Infectionmentioning

confidence: 99%

Opioids and Viral Infections: A Double-Edged Sword

et al. 2016

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“…In addition to the central nervous system and the heart, δ-opioid receptors are highly expressed in liver and liver cancer cells (6,7). Furthermore, the δ-opioid receptor has been found to have a significant role in the occurrence and development of liver diseases, including hepatoma, viral hepatitis and hepatic cirrhosis (7)(8)(9). H 2 O 2 is commonly used to induce apoptosis (10).…”

Section: Introductionmentioning

confidence: 99%

Activated δ-opioid receptors inhibit hydrogen peroxide-induced apoptosis in liver cancer cells through the PKC/ERK signaling pathway

Jia

Sun

Ling

et al. 2014

Molecular Medicine Reports

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Apoptotic liver cancer cells have important roles in liver tumorigenesis and liver cancer progression. Recent studies have shown that δ‑opioid receptors are highly expressed in human liver and liver cancer cells. The present study aimed to investigate the role of activated δ‑opioid receptors on human liver cancer cell apoptosis and its interrelation with the mitochondria and the protein kinase C/extracellular‑signal‑regulated kinase (PKC/ERK) signaling pathway. H2O2 was used to induce apoptosis in human liver cancer cells. During apoptosis, mitochondrial transmembrane potentials were observed to decrease, cytochrome c expression was found to increase and B cell lymphoma 2 (Bcl‑2) expression decreased. These findings suggested that H2O2‑induced apoptosis was mediated through the mitochondrial pathway. Of note, activated δ‑opioid receptors were observed to inhibit H2O2‑induced apoptosis in human liver cancer cells. Following δ‑opioid receptor activation, the number of apoptotic liver cancer cells decreased, mitochondrial transmembrane potentials were restored, cytoplasmic cytochrome c and Bcl‑2‑associated X protein expression decreased and Bcl‑2 expression increased. These data suggested that δ‑opioid receptor activation inhibited mitochondria‑mediated apoptosis. In addition, activation of δ‑opioid receptors was observed to increase the expression of PKC and ERK in human liver cancer cells. Furthermore, upon inhibition of the PKC/ERK signaling pathway, the protective effect associated with the δ‑opioid receptor on liver cancer cell apoptosis was inhibited, which was not associated with the status of δ‑opioid receptor activation. These findings suggested that the PKC/ERK signaling pathway has an important role in δ‑opioid receptor‑mediated inhibition of apoptosis in human liver cancer cells.

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“…MENK is expressed in hepatocytes exposed to stresses induced by the hepatitis virus, autoimmune hepatitis, primary biliary cirrhosis, and cholestatic liver disease 13–15. It is thought to enhance the replication of the hepatitis C virus in the human liver and to interfere with the therapeutic effect of interferons 13. MENK induces hepatic fibrogenesis by activating hepatic stellate cells,16 and may also modulate T-cell function in the liver in hepatitis, and in CRCs 17.…”

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confidence: 99%