SAM disminuye la replicación de VHC mediante regulación de procesos celulares
Palabras clave:
VHC, SAM, GSH, proteasoma, Estrés oxidativoResumen
El agente etiológico de la hepatitis C crónica es el VHC, el cual es un virus que desencadena estrés oxidativo celular; sin embargo, el mecanismo involucrado es desconocido. En este trabajo se encontró que s-adenosil metionina (SAM) inhibe la replicación del VHC a nivel transcripcional y traduccional a una dosis de 1mM durante 24-72 h. Se demostró que SAM es capaz de modular negativamente la actividad de quimotripsina del proteasoma y el efecto se potencia al combinar un inhibidor del proteasoma (MG132) con SAM. Además, la adición de SAM estimula la biosíntesis de GSH en el contexto de la infección por VHC.
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Arif, A., Levine, R., Sanderson, S. (2003). Regression of fibrosis in chronic hepatitis C after therapy with interferon and ribavirin. Dig Dis Sci. 48(7):1425-1430.
EASL (2015). Easl recommendations on treatment of hepatitis C 2015. J Hepatol. 2015;61(2):373-395. Doi: 10.1016/j.jhep.2014.05.001
FDA. (2013). FDA approves Sovaldi for chronic hepatitis C. Disponible en: http://www.fda.gov/newsevents/newsroom/pressannouncements/ucm377888.htm
Feld, J.J., et al. (2011). S-adenosyl methionine improves early viral responses and interferon-stimulated gene induction in hepatitis C nonresponders. Gastroenterology, 140(3):830-839. doi: 10.1053/j.gastro.2010.09.010
Gil, M.P., et al. (2001). Biologic consequences of Stat1- independent IFN signaling. Proc Natl Acad Sci. 98:6680-6685.
Krishnan, P., Beyer, J., Koev, G. (2012). Antiviral activity and resistance profiles for ABT-267, a Novel HCV NS5A inhibitor, in vitro and during 3-day monotherapy in hcv genotype-1 (gt1)-infected treatment-naive subjects. Hepatology, 56:1069A.
Lee, H.S., et al. (2014). SUMOylation of nonstructural 5A protein regulates hepatitis C virus replication. J Viral Hepat., 21(10):e108-e117. doi: 10.1111/jvh.12241.
Lindenbach, B.D., y Rice, C.M. (2005). Unravelling hepatitis C virus replication from genome to function. Nature, 436(7053):933-938. doi: 10.1038/nature04077
Lohmann, V., et al. (1999). Replication of Subgenomic Hepatitis C Virus RNAs in a Hepatoma Cell Line. Science, 285(5424):110-113. doi: 10.1126/science.285.5424.110
Lozano-Sepulveda, S.A., et al. (2016). S-adenosyl-L-methionine modifies antioxidant-enzymes, glutathione-biosynthesis and methionine adenosyltransferases-1/2 in hepatitis C virus-expressing cells. World J Gastroenterol, 22(14):3746-3757. doi: 10.3748/wjg.v22.i14.3746
Moriishi, K., et al. (2010). Involvement of PA28gamma in the propagation of hepatitis C virus. Hepatology, 52:411-420.
Munakata, T., et al. (2007). Hepatitis C virus induces E6AP-dependent degradation of the retinoblastoma protein. PLoS Pathog., 3:1335-1347.
Ramana, C.V., et al. (2001). Stat1-independent regulation of gene expression in response to IFN-gamma. Proc Natl Acad Sci., 98:6674-6679.
Rivas E., A.M., et al. (2012). Cu/Zn superoxide dismutase (SOD1) induction is implicated in the antioxidative and antiviral activity of acetylsalicylic acid in HCV-expressing cells. AJP Gastrointest Liver Physiol., 302(11):G1264-G1273. doi: 10.1152/ajpgi.00237.2011
Shirakura, M., et al. (2007). E6AP Ubiquitin Ligase Mediates Ubiquitylation and Degradation of Hepatitis C Virus Core Protein. J Virol., 1(3):1174-1185. doi: 10.1128/JVI.01684-06
Tamori, A., Enomoto, M., y Kawada, N. (2016). Recent Advances in Antiviral Therapy for Chronic Hepatitis C. Mediators Inflamm, Vol. 2016, Article ID 6841628, 11 pages, 2016. doi:10.1155/2016/6841628.
Tomasi, M.L., et al. (2012). S-adenosylmethionine Regulates Ubiquitin-Conjugating Enzyme 9 Protein Expression and Sumoylation in Murine Liver and Human Cancers. Hepatology, 56(3):982-993. doi: 10.1002/hep.25701
US Food and Drug Administration. (2015). FDA Approves New Treatment for Chronic Hepatitis C Genotype 3 Infections. Disponible en: https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm455888.htm
Valdespino, J.L., et al. (2007). Seroprevalencia de la hepatitis C en adultos de México: ¿un problema de salud pública emergente? Salud Publica Mex., 49 (SUPPL. 3):395-403. doi:10.1590/S0036-36342007000900011.
Wang, Y., et al. (2013). Induction of interferon-γ contributes to Toll-like receptor-3 activated hepatic stellate cell-mediated hepatitis C virus inhibition in hepatocytes. J Viral Hepat., 20(6):385-394. doi: 10.1111/jvh.12040
WHO (2015, julio). Hepatitis C Fact sheet N°164. Disponible en: http://www.who.int/mediacentre/factsheets/fs164/en/
