TIMP‐1 deficiency leads to lethal partial hepatic ischemia and reperfusion injury

Sergio Duarte, Takashi Hamada, Naohisa Kuriyama, Ronald W. Busuttil, Ana J. Coito – 12 March 2012 – Hepatic ischemia and reperfusion injury (IRI) remains an important challenge in clinical orthotopic liver transplantation (OLT). Tissue inhibitor of metalloproteinase‐1 (TIMP‐1) is the major endogenous regulator of matrix metalloproteinase‐9 (MMP‐9). In this study we investigated the functional significance of TIMP‐1 expression in a well‐established mouse model of partial liver IRI.

Hepatic activation of IKK/NFκB signaling induces liver fibrosis via macrophage‐mediated chronic inflammation

Yoshiaki Sunami, Frank Leithäuser, Sarah Gul, Katja Fiedler, Nurdan Güldiken, Sigrid Espenlaub, Karl‐Heinz Holzmann, Nora Hipp, Anca Sindrilaru, Tom Luedde, Bernd Baumann, Sebastian Wissel, Florian Kreppel, Marion Schneider, Karin Scharffetter‐Kochanek, Stefan Kochanek, Pavel Strnad, Thomas Wirth – 12 March 2012 – Liver damage in humans is induced by various insults including alcohol abuse, hepatitis B/C virus infection, autoimmune or metabolic disorders and, when persistent, leads to development of liver fibrosis.

Human immunodeficiency virus protease inhibitors modulate Ca2+ homeostasis and potentiate alcoholic stress and injury in mice and primary mouse and human hepatocytes

Eddy Kao, Masao Shinohara, Min Feng, Mo Yin Lau, Cheng Ji – 10 March 2012 – A portion of human immunodeficiency virus (HIV)‐infected patients undergoing protease inhibitor (PI) therapy concomitantly consume or abuse alcohol leading to hepatic injury. The underling mechanisms are not known. We hypothesize that HIV PIs aggravate alcohol‐induced liver injury through an endoplasmic reticulum (ER) stress mechanism. To address this, we treated mice, primary mouse hepatocytes (PMHs), and primary human hepatocytes (PHHs) with alcohol and the HIV PIs ritonavir (RIT) and lopinavir (LOP).

S‐adenosyl methionine regulates ubiquitin‐conjugating enzyme 9 protein expression and sumoylation in murine liver and human cancers

Maria Lauda Tomasi, Ivan Tomasi, Komal Ramani, Rosa Maria Pascale, Jun Xu, Pasquale Giordano, José M. Mato, Shelly C. Lu – 10 March 2012 – Ubiquitin‐conjugating enzyme 9 (Ubc9) is required for sumoylation and is overexpressed in several malignancies, but its expression in hepatocellular carcinoma (HCC) is unknown. Hepatic S‐adenosyl methionine (SAMe) levels decrease in methionine adenosyltransferase 1A (Mat1a) knockout (KO) mice, which develop HCC, and in ethanol‐fed mice.

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