PCSK9 impedes hepatitis C virus infection in vitro and modulates liver CD81 expression

Patrick Labonté, Syntia Begley, Carl Guévin, Marie‐Claude Asselin, Nasha Nassoury, Gaétan Mayer, Annik Prat, Nabil G. Seidah – 23 June 2009 – Human PCSK9 is known to enhance the degradation of membrane‐bound receptors such as the hepatocyte low‐density lipoprotein receptor (LDLR), ApoER2, and very low‐density lipoprotein receptor. Because the LDLR is suspected to be involved in hepatitis C virus (HCV) entry, we also tested whether PCSK9 can affect the levels of CD81, a major HCV receptor.

Protein or amino acid deprivation differentially regulates the hepatic forkhead box protein A (FOXA) genes through an activating transcription factor‐4–independent pathway

Nan Su, Michelle M. Thiaville, Keytam Awad, Altin Gjymishka, Jason O. Brant, Thomas P. Yang, Michael S. Kilberg – 23 June 2009 – The FOXA (forkhead box A) proteins (FOXA1, FOXA2, and FOXA3) play a critical role in the development of the liver, and they also regulate metabolism in adult hepatic tissue. The liver responds to changes in nutrient availability by initiating a number of stress signaling pathways. The present studies demonstrated that in mouse dams fed a low‐protein diet hepatic expression of FOXA2 and FOXA3 messenger RNA, but not FOXA1, was induced.

Hepatitis B and C virus coinfection: A novel model system reveals the absence of direct viral interference

Pantxika Bellecave, Jérôme Gouttenoire, Markus Gajer, Volker Brass, George Koutsoudakis, Hubert E. Blum, Ralf Bartenschlager, Michael Nassal, Darius Moradpour – 23 June 2009 – Coinfection with hepatitis B virus (HBV) and hepatitis C virus (HCV) has been associated with severe liver disease and frequent progression to cirrhosis and hepatocellular carcinoma. Clinical evidence suggests reciprocal replicative suppression of the two viruses, or viral interference. However, interactions between HBV and HCV have been difficult to study due to the lack of appropriate model systems.

Targeting heat shock protein 90 with non‐quinone inhibitors: A novel chemotherapeutic approach in human hepatocellular carcinoma

Marco Breinig, Eloisi Caldas‐Lopes, Benjamin Goeppert, Mona Malz, Ralf Rieker, Frank Bergmann, Peter Schirmacher, Matthias Mayer, Gabriela Chiosis, Michael André Kern – 23 June 2009 – The inhibition of heat shock protein 90 (Hsp90) has emerged as a promising antineoplastic strategy in diverse human malignancies. Hsp90 has been predicted to be involved in hepatocellular carcinoma (HCC) development; however, its role in hepatocarcinogenesis remains elusive.

Toll‐like receptor 3 signaling attenuates liver regeneration

Elina Zorde‐Khvalevsky, Rinat Abramovitch, Hila Barash, Irit Spivak‐Pohis, Ludmila Rivkin, Jacob Rachmilewitz, Eithan Galun, Hilla Giladi – 23 June 2009 – The current model for liver regeneration suggests that cell damage triggers Toll‐like receptor (TLR) signaling via MyD88, leading to the induction of nuclear factor κB (NF‐κB) and secretion of inflammatory cytokines that in turn prime liver regeneration.

Inhibiting glycosphingolipid synthesis ameliorates hepatic steatosis in obese mice

Hongmei Zhao, Malgorzata Przybylska, I‐Huan Wu, Jinhua Zhang, Panagiotis Maniatis, Joshua Pacheco, Peter Piepenhagen, Diane Copeland, Cynthia Arbeeny, James A. Shayman, Johannes M. Aerts, Canwen Jiang, Seng H. Cheng, Nelson S. Yew – 23 June 2009 – Steatosis in the liver is a common feature of obesity and type 2 diabetes and the precursor to the development of nonalcoholic steatohepatitis (NASH), cirrhosis, and liver failure. It has been shown previously that inhibiting glycosphingolipid (GSL) synthesis increases insulin sensitivity and lowers glucose levels in diabetic rodent models.

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