Inhibition of natural killer cells protects the liver against acute injury in the absence of glycine N‐methyltransferase

Laura Gomez‐Santos, Zigmund Luka, Conrad Wagner, Sara Fernandez‐Alvarez, Shelly C. Lu, Jose M. Mato, Maria L. Martinez‐Chantar, Naiara Beraza – 5 March 2012 – Glycine N‐methyltransferase (GNMT) catabolizes S‐adenosylmethionine (SAMe), the main methyl donor of the body. Patients with cirrhosis show attenuated GNMT expression, which is absent in hepatocellular carcinoma (HCC) samples. GNMT−/− mice develop spontaneous steatosis that progresses to steatohepatitis, cirrhosis, and HCC.

TAT‐apoptosis repressor with caspase recruitment domain protein transduction rescues mice from fulminant liver failure

Junfeng An, Christoph Harms, Gisela Lättig‐Tünnemann, Gernot Sellge, Ana D. Mandić, Yann Malato, Arnd Heuser, Matthias Endres, Christian Trautwein, Stefan Donath – 5 March 2012 – Acute liver failure (ALF) is associated with massive hepatocyte cell death and high mortality rates. Therapeutic approaches targeting hepatocyte injury in ALF are hampered by the activation of distinct stimulus‐dependent pathways, mechanism of cell death, and a limited therapeutic window.

Frequency, clinical presentation, and outcomes of drug‐induced liver injury after liver transplantation

Stepan Sembera, Craig Lammert, Jayant A. Talwalkar, Schuyler O. Sanderson, John J. Poterucha, J. Eileen Hay, Russell H. Wiesner, Gregory J. Gores, Charles B. Rosen, Julie K. Heimbach, Michael R. Charlton – 5 March 2012 – Drug‐induced liver injury (DILI) is increasingly being recognized as a common cause of acute hepatitis. The clinical impact of DILI after liver transplantation (LT) is not known. The aim of this study was to describe the frequency, clinical presentation, and outcomes of DILI in LT recipients.

Histone deacetylase 6 functions as a tumor suppressor by activating c‐Jun NH2‐terminal kinase‐mediated beclin 1‐dependent autophagic cell death in liver cancer

Kwang Hwa Jung, Ji Heon Noh, Jeong Kyu Kim, Jung Woo Eun, Hyun Jin Bae, Young Gyoon Chang, Min Gyu Kim, Won Sang Park, Jung Young Lee, Sang‐Yeop Lee, In‐Sun Chu, Suk Woo Nam – 5 March 2012 – Ubiquitin‐binding histone deacetylase 6 (HDAC6) is uniquely endowed with tubulin deacetylase activity and plays an important role in the clearance of misfolded protein by autophagy. In cancer, HDAC6 has become a target for drug development due to its major contribution to oncogenic cell transformation.

Hepatocyte senescence in vivo following preconditioning for liver repopulation

Maria Paola Serra, Fabio Marongiu, Marcella Sini, Ezio Laconi – 5 March 2012 – In the retrorsine (RS)‐based model of massive liver repopulation, preexposure to this naturally occurring alkaloid is sufficient to prime normal host parenchymal cells to be slowly replaced by transplanted normal hepatocytes. The basis for this striking effect is yet to be fully elucidated. In the present studies the possible involvement of cell senescence was investigated.

Androgen pathway stimulates MicroRNA‐216a transcription to suppress the tumor suppressor in lung cancer‐1 gene in early hepatocarcinogenesis

Po‐Jen Chen, Shiou‐Hwei Yeh, Wan‐Hsin Liu, Chen‐Ching Lin, Hsuan‐Cheng Huang, Chi‐Ling Chen, Ding‐Shinn Chen, Pei‐Jer Chen – 5 March 2012 – Deregulation of microRNAs (miRNAs) is common in advanced human hepatocellular carcinoma (HCC); however, the ones involved in early carcinogenesis have not yet been investigated. By examining the expression of 22 HCC‐related miRNAs between precancerous and cancerous liver tissues, we found miR‐216a and miR‐224 were significantly up‐regulated, starting from the precancerous stage.

Disruption of hemochromatosis protein and transferrin receptor 2 causes iron‐induced liver injury in mice

Roheeth D. Delima, Anita C.G. Chua, Janina E.E. Tirnitz‐Parker, Eng K. Gan, Kevin D. Croft, Ross M. Graham, John K. Olynyk, Debbie Trinder – 2 March 2012 – Mutations in hemochromatosis protein (HFE) or transferrin receptor 2 (TFR2) cause hereditary hemochromatosis (HH) by impeding production of the liver iron‐regulatory hormone, hepcidin (HAMP). This study examined the effects of disruption of Hfe or Tfr2, either alone or together, on liver iron loading and injury in mouse models of HH.

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