P-Nrf2 was constitutively increased in the nucleus of HPI cell

Of them, up-regulation of SLC1A5, SLC7A1, and SLC7A11 were remarkable, possibly leading to the increase of amino acid intake. Notably, SLC7A11, which is a cysteine transporter, confers resistance against oxidative stress and is related to multiple cancers. According to the immunoblot analyses, Maf G was increased in HPI cell, but the extent was slight. Thus we suggest that translocation of p-Nrf2, active form of Nrf2, might play a more important role in the expression of the genes, which contribute to anti-apoptosis and HCV persistence. Actually, P-Nrf2 was constitutively increased in the nucleus of HPI cell and the genes under its control were also constitutively activated. Although precise mechanism is unclear, it is speculated that some genetic or epigenetic alterations could have occurred during the long-term culture and the clonal selections N6022 affecting the Nrf2/Maf system. Drastic reduction of LDs and lipid contents by the Nrf2 knockdown indicates that steatosis is dependent of Nrf2 in HPI cell. Additionally, we demonstrated that knockdown of Nrf2 reduced HCV infection. Reduction of its target gene expression by the Nrf2 knockdown varied, suggesting that extent of transactivation by Nrf2 and protein stability is dependent on an individual gene. Since HCV infectious cycle is closely related to lipid metabolism and LDs, reduction of HCV by the Nrf2 knockdown might have been caused via impairment of lipid metabolism. We need to know which target gene are more responsible for HCV infection and lipid metabolism. Emerging anti-HCV drugs will bring about further improvement in sustained virological response in HCV patients. Recent study showed the risk of HCC remains even after sustained virological response. Genetic or epigenetic alterations that had occurred in the hepatocytes in the HCV patients for long term chronic infection may increase HCC risk. Nrf2 and/or its target gene might be involved in candidates of such genetic alteration, because Nrf2 is activated in many cancers and would favor cell growth arrest of cancers Thus, genetic experiments like ultra-deep sequencing will be needed in Dapoxetine hydrochloride search of such alterations in both HPI cell and clinical HCC.

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