Hepatic glycosphingolipid deficiency and liver function in mice

Richard Jennemann, Ulrike Rothermel, Shijun Wang, Roger Sandhoff, Sylvia Kaden, Ruud Out, Theo J. van Berkel, Johannes M. Aerts, Karen Ghauharali, Carsten Sticht, Hermann‐Josef Gröne – 22 April 2010 – Recent studies have reported that glycosphingolipids (GSLs) might be involved in obesity‐induced insulin resistance. Those reports suggested that inhibition of GSL biosynthesis in animals ameliorated insulin resistance accompanied by improved glycemic control and decreased liver steatosis in obese mice. In addition, pharmacologic GSL depletion altered hepatic secretory function.

Clearance of hepatitis B surface antigen and risk of hepatocellular carcinoma in a cohort chronically infected with hepatitis B virus

Josephine Simonetti, Lisa Bulkow, Brian J. McMahon, Chriss Homan, Mary Snowball, Susan Negus, James Williams, Stephen E. Livingston – 22 April 2010 – Some individuals who are chronically infected with hepatitis B virus (HBV) eventually lose hepatitis B surface antigen (HBsAg). Hepatocellular carcinoma (HCC) has been demonstrated to occur in a few patients after loss of HBsAg. Neither factors associated with loss of HBsAg nor the incidence of HCC thereafter have been clearly elucidated.

Down‐regulation of tyrosine aminotransferase at a frequently deleted region 16q22 contributes to the pathogenesis of hepatocellular carcinoma

Li Fu, Sui‐Sui Dong, Yi‐Wu Xie, Lai‐Shan Tai, Leilei Chen, Kar Lok Kong, Kwan Man, Dan Xie, Yan Li, Yingduan Cheng, Qian Tao, Xin‐Yuan Guan – 22 April 2010 – Loss of 16q is one of the most frequent alterations in many malignancies including hepatocellular carcinomas (HCC), suggesting the existence of a tumor suppressor gene (TSG) within the frequently deleted region. In this report we describe the identification and characterization of one candidate TSG, tyrosine aminotransferase gene (TAT), at 16q22.1.

Accelerated liver regeneration and hepatocarcinogenesis in mice overexpressing serine‐45 mutant β‐catenin

Kari N. Nejak‐Bowen, Michael D. Thompson, Sucha Singh, William C. Bowen, Mohd Jamal Dar, Jaspal Khillan, Chunsun Dai, Satdarshan P.S. Monga – 22 April 2010 – The Wnt/β‐catenin pathway is implicated in the pathogenesis of hepatocellular cancer (HCC). We developed a transgenic mouse (TG) in the FVB strain that overexpresses Ser45‐mutated‐β‐catenin in hepatocytes to study the effects on liver regeneration and cancer. In the two independent TG lines adult mice show elevated β‐catenin at hepatocyte membrane with no increase in the Wnt pathway targets cyclin‐D1 or glutamine synthetase.

MicroRNA‐196 represses Bach1 protein and hepatitis C virus gene expression in human hepatoma cells expressing hepatitis C viral proteins

Weihong Hou, Qing Tian, Jianyu Zheng, Herbert L. Bonkovsky – 22 April 2010 – Hepatitis C virus (HCV) directly induces oxidative stress and liver injury. Bach1, a basic leucine zipper mammalian transcriptional repressor, negatively regulates heme oxygenase 1 (HMOX1), a key cytoprotective enzyme that has antioxidant and anti‐inflammatory activities. microRNAs (miRNAs) are small noncoding RNAs (≈22 nt) that are important regulators of gene expression. Whether and how miRNAs regulate Bach1 or HCV are largely unknown.

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