Combined deletion of Hfe and transferrin receptor 2 in mice leads to marked dysregulation of hepcidin and iron overload

Daniel F. Wallace, Lesa Summerville, Emily M. Crampton, David M. Frazer, Gregory J. Anderson, V. Nathan Subramaniam – 20 November 2009 – Hepcidin is a central regulator of iron homeostasis. HFE and transferrin receptor 2 (TFR2) are mutated in adult‐onset forms of hereditary hemochromatosis and regulate the expression of hepcidin in response to iron. Whether they act through the same or parallel pathways is unclear. To investigate this, we generated a mouse model with deletion of both Hfe and Tfr2 genes by crossing Hfe and Tfr2 null mice on a genetically identical background.

Ikappa B kinaseβ/nuclear factor‐κB activation controls the development of liver metastasis by way of interleukin‐6 expression

Shin Maeda, Yohko Hikiba, Kei Sakamoto, Hayato Nakagawa, Yoshihiro Hirata, Yoku Hayakawa, Ayako Yanai, Keiji Ogura, Michael Karin, Masao Omata – 20 November 2009 – Nuclear factor kappaB (NF‐κB) plays an important role in the regulation of innate immune responses, apoptosis, inflammation, and oncogenesis. NF‐κB activation in the liver was observed after intrasplenic administration of a lung carcinoma cell line, LLC, which induces liver metastasis.

Reduced expression of ATP7B affected by Wilson disease–causing mutations is rescued by pharmacological folding chaperones 4‐phenylbutyrate and curcumin

Peter V. E. van den Berghe, Janneke M. Stapelbroek, Elmar Krieger, Prim de Bie, Stan F. J. van de Graaf, Reinoud E. A. de Groot, Ellen van Beurden, Ellen Spijker, Roderick H. J. Houwen, Ruud Berger, Leo W. J. Klomp – 20 November 2009 – Wilson disease (WD) is an autosomal recessive copper overload disorder of the liver and basal ganglia. WD is caused by mutations in the gene encoding ATP7B, a protein localized to the trans‐Golgi network that primarily facilitates hepatic copper excretion.

Characterization of resistance to the protease inhibitor boceprevir in hepatitis C virus–infected patients

Simone Susser, Christoph Welsch, Yalan Wang, Markus Zettler, Francisco S. Domingues, Ursula Karey, Eric Hughes, Robert Ralston, Xiao Tong, Eva Herrmann, Stefan Zeuzem, Christoph Sarrazin – 20 November 2009 – Boceprevir is a hepatitis C virus (HCV) nonstructural protein (NS) 3/4A protease inhibitor that is currently being evaluated in combination with peginterferon alfa‐2b and ribavirin in phase 3 studies. The clinical resistance profile of boceprevir is not characterized in detail so far. The NS3 protease domain of viral RNA was cloned from HCV genotype 1–infected patients (n = 22).

The plasma lipidomic signature of nonalcoholic steatohepatitis

Puneet Puri, Michelle M. Wiest, Onpan Cheung, Faridoddin Mirshahi, Carol Sargeant, Hae‐Ki Min, Melissa J. Contos, Richard K. Sterling, Michael Fuchs, Huiping Zhou, Steven M. Watkins, Arun J. Sanyal – 20 November 2009 – Specific alterations in hepatic lipid composition characterize the spectrum of nonalcoholic fatty liver disease (NAFLD), which extends from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). However, the plasma lipidome of NAFLD and whether NASH has a distinct plasma lipidomic signature are unknown.

Antiviral effects of the interferon‐induced protein guanylate binding protein 1 and its interaction with the hepatitis C virus NS5B protein

Yasuhiro Itsui, Naoya Sakamoto, Sei Kakinuma, Mina Nakagawa, Yuko Sekine‐Osajima, Megumi Tasaka‐Fujita, Yuki Nishimura‐Sakurai, Gouki Suda, Yuko Karakama, Kako Mishima, Machi Yamamoto, Takako Watanabe, Mayumi Ueyama, Yusuke Funaoka, Seishin Azuma, Mamoru Watanabe – 20 November 2009 – Interferons (IFNs) and the interferon‐stimulated genes (ISGs) play a central role in antiviral responses against hepatitis C virus (HCV) infection.

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