Translocation of iron from lysosomes into mitochondria is a key event during oxidative stress‐induced hepatocellular injury

Akira Uchiyama, Jae‐Sung Kim, Kazuyoshi Kon, Hartmut Jaeschke, Kenichi Ikejima, Sumio Watanabe, John J. Lemasters – 28 October 2008 – Iron overload exacerbates various liver diseases. In hepatocytes, a portion of non‐heme iron is sequestered in lysosomes and endosomes. The precise mechanisms by which lysosomal iron participates in hepatocellular injury remain uncertain. Here, our aim was to determine the role of intracellular movement of chelatable iron in oxidative stress‐induced killing to cultured hepatocytes from C3Heb mice and Sprague‐Dawley rats.

Rab4 facilitates cyclic adenosine monophosphate–stimulated bile acid uptake and Na+‐taurocholate cotransporting polypeptide translocation

Christopher M. Schonhoff, Krishna Thankey, Cynthia R.L. Webster, Yoshiyuki Wakabayashi, Allan W. Wolkoff, M. Sawkat Anwer – 28 October 2008 – Cyclic adenosine monophosphate (cAMP) stimulates hepatic bile acid uptake by translocating sodium‐taurocholate (TC) cotransporting polypeptide (Ntcp) from an endosomal compartment to the plasma membrane. Rab4 is associated with early endosomes and involved in vesicular trafficking. This study was designed to determine the role of Rab4 in cAMP‐induced TC uptake and Ntcp translocation.

The angiogenic makeup of human hepatocellular carcinoma does not favor vascular endothelial growth factor/angiopoietin‐driven sprouting neovascularization

Wenjiao Zeng, Annette S.H. Gouw, Marius C. van den Heuvel, Peter J. Zwiers, Pieter E. Zondervan, Sibrand Poppema, Nong Zhang, Inge Platteel, Koert P. de Jong, Grietje Molema – 28 October 2008 – Quantitative data on the expression of multiple factors that control angiogenesis in hepatocellular carcinoma (HCC) are limited. A better understanding of the mechanisms underlying angiogenesis in HCC will improve the rational choice of anti‐angiogenic treatment.

Is there a meaningful serum hepatitis B virus DNA cutoff level for therapeutic decisions in hepatitis B e antigen–negative chronic hepatitis B virus infection?

George V. Papatheodoridis, Emanuel K. Manesis, Spilios Manolakopoulos, Ioannis S. Elefsiniotis, John Goulis, John Giannousis, Antonios Bilalis, Georgia Kafiri, Dimitrios Tzourmakliotis, Athanasios J. Archimandritis – 28 October 2008 – The diagnosis of hepatitis B e antigen (HBeAg)‐negative chronic hepatitis B indicating therapeutic intervention currently requires serum hepatitis B virus (HBV) DNA ≥2,000 IU/mL.

Evaluation of previously nonscreened hereditary hemorrhagic telangiectasia patients shows frequent liver involvement and early cardiac consequences

Rodica Gincul, Gaetan Lesca, Bénédicte Gelas‐Dore, Nathalie Rollin, Martine Barthelet, Sophie Dupuis‐Girod, Franck Pilleul, Sophie Giraud, Henri Plauchu, Jean‐Christophe Saurin – 28 October 2008 – Hereditary hemorrhagic telangiectasia (HHT) is a genetic disease characterized by cutaneous, mucosal, and sometimes visceral arteriovenous malformations. Severe hepatic manifestations have been characterized in a subgroup of patients, but few data are available in previously nonscreened patients. We prospectively evaluated liver involvement and its cardiac consequences in such patients.

Heme oxygenase‐1 suppresses hepatitis C virus replication and increases resistance of hepatocytes to oxidant injury

Zhaowen Zhu, Anne T. Wilson, M. Meleah Mathahs, Feng Wen, Kyle E. Brown, Bruce A. Luxon, Warren N. Schmidt – 28 October 2008 – Oxidative injury to hepatocytes occurs as a result of hepatitis C virus (HCV) infection and replication. Modulation of host cell antioxidant enzymes such as heme oxygenase‐1 (HO‐1) may be useful therapeutically to minimize cellular injury, reduce viral replication, and attenuate liver disease. In this report, we evaluated the effects of HO‐1 overexpression on HCV replication and hepatocellular injury.

Functional alterations of liver innate immunity of mice with aging in response to CpG‐oligodeoxynucleotide

Toshinobu Kawabata, Manabu Kinoshita, Akihito Inatsu, Yoshiko Habu, Hiroyuki Nakashima, Nariyoshi Shinomiya, Shuhji Seki – 28 October 2008 – Immune functions of liver natural killer T (NKT) cells induced by the synthetic ligand α‐galactosylceramide enhanced age‐dependently; hepatic injury and multiorgan dysfunction syndrome (MODS) induced by ligand‐activated NKT cells were also enhanced. This study investigated how aging affects liver innate immunity after common bacteria DNA stimulation.

Hepatitis C virus–induced oxidative stress suppresses hepcidin expression through increased histone deacetylase activity

Kouichi Miura, Kojiro Taura, Yuzo Kodama, Bernd Schnabl, David A. Brenner – 28 October 2008 – Chronic hepatitis C is characterized by iron accumulation in the liver, and excessive iron is hepatotoxic. However, the mechanism by which hepatitis C virus (HCV) regulates iron metabolism is poorly understood. Hepcidin plays a pivotal role as a negative regulator of iron absorption. The aim of the current study was to elucidate the mechanisms that govern hepcidin expression by HCV.

Treatment of chronic hepatitis C in hemodialysis patients

Marina Berenguer – 28 October 2008 – Hepatitis C virus (HCV) infection is especially problematic in patients with end‐stage renal disease (ESRD) who are undergoing hemodialysis. Rates of HCV infection are higher among hemodialysis patients than in the general population, and several routes of transmission are thought to stem from the dialysis unit. Management of chronic hepatitis C is also more complicated in hemodialysis patients because of altered pharmacokinetics and a predisposition for drug‐related toxicity, particularly ribavirin‐induced anemia.

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