Lin Yi-Ching, Wu Hui-Chung, Liao Chen-Chung, Chou Yi-Chih, Pan Shwu-Fen, Chiu Chi-Ming
Department of Biotechnology, Ming Chuan University, Guishan 333, Taiwan.
Proteomics Research Center, National Yang-Ming University, Taipei 11221, Taiwan.
Mediators Inflamm. 2015;2015:392471. doi: 10.1155/2015/392471. Epub 2015 Feb 26.
Nampt/visfatin acts in both intracellular and extracellular compartments to regulate multiple biological roles, including NAD metabolism, cancer, inflammation, and senescence. However, its function in chronic inflammation and carcinogenesis in hepatocellular carcinoma (HCC) has not been well-defined. Here we use Huh-7 hepatoma cells as a model to determine how Nampt/visfatin affects cellular survival under oxidative stress. We found that the transition of Nampt/visfatin from intracellular into extracellular form was induced by H2O2 treatment in 293T cells and confirmed that this phenomenon was not due to cell death but through the secretion of Nampt/visfatin. In addition, Nampt/visfatin suppressed cell viability in oxidative treatment in Huh-7 cells and acted on the inhibition of hepatoma cell growth. Oxidative stress also reduced the Nampt-mediated activation of NF-κB gene expression. In this study, we identify a novel feature of Nampt/visfatin which functions as an adipokine that can be secreted upon cellular stress. Our results provide an example to understand how adipokine interacts with chemotherapeutic treatment by oxidative stress in HCC.
烟酰胺磷酸核糖转移酶/内脂素在细胞内和细胞外区室中均发挥作用，以调节多种生物学功能，包括烟酰胺腺嘌呤二核苷酸（NAD）代谢、癌症、炎症和衰老。然而，其在肝细胞癌（HCC）的慢性炎症和致癌过程中的功能尚未明确界定。在此，我们以Huh-7肝癌细胞为模型，来确定烟酰胺磷酸核糖转移酶/内脂素如何在氧化应激下影响细胞存活。我们发现，在293T细胞中，H2O2处理可诱导烟酰胺磷酸核糖转移酶/内脂素从细胞内形式转变为细胞外形式，并证实这种现象并非由于细胞死亡，而是通过烟酰胺磷酸核糖转移酶/内脂素的分泌所致。此外，烟酰胺磷酸核糖转移酶/内脂素在氧化处理中抑制了Huh-7细胞的活力，并对肝癌细胞生长起抑制作用。氧化应激还降低了烟酰胺磷酸核糖转移酶介导的核因子κB（NF-κB）基因表达的激活。在本研究中，我们确定了烟酰胺磷酸核糖转移酶/内脂素的一个新特性，即其作为一种脂肪因子，可在细胞应激时分泌。我们的研究结果为理解脂肪因子如何与HCC中氧化应激的化疗治疗相互作用提供了一个实例。
