Knockout of myeloid cell leukemia-1 induces liver damage and increases apoptosis susceptibility of murine hepatocytes.

Hepatology : Official Journal of the American Association for the Study of Liver Diseases
Binje VickHenning Schulze-Bergkamen

Abstract

Myeloid cell leukemia-1 (Mcl-1) is an antiapoptotic member of the Bcl-2 protein family. It interacts with proapoptotic Bcl-2 family members, thereby inhibiting mitochondrial activation and induction of apoptosis. Mcl-1 is essential for embryonal development and the maintenance of B cells, T cells, and hematopoietic stem cells. We have recently shown that induction of Mcl-1 by growth factors rescues primary human hepatocytes from CD95-mediated apoptosis. This prompted us to further analyze the relevance of Mcl-1 for hepatocellular homeostasis. Therefore, we generated a hepatocyte-specific Mcl-1 knockout mouse (Mcl-1(flox/flox)-AlbCre). Deletion of Mcl-1 in hepatocytes results in liver cell damage caused by spontaneous induction of apoptosis. Livers of Mcl-1(flox/flox)-AlbCre mice are smaller compared to control littermates, due to higher apoptosis rates. As a compensatory mechanism, proliferation of hepatocytes is enhanced in the absence of Mcl-1. Importantly, hepatic pericellular fibrosis occurs in Mcl-1 negative livers in response to chronic liver damage. Furthermore, Mcl-1(flox/flox)-AlbCre mice are more susceptible to hepatocellular damage induced by agonistic anti-CD95 antibodies or concanavalin A. The present study provide...Continue Reading

References

Jul 1, 1992·The Journal of Clinical Investigation·G TiegsA Wendel
Mar 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·L BraunN Fausto
Nov 1, 1995·The Journal of Experimental Medicine·P R GalleL Runkel
Apr 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·K M KozopasR W Craig
Aug 26, 1993·Nature·J OgasawaraS Nagata
Apr 16, 1998·Biochemical and Biophysical Research Communications·K KosaiT Nakamura
Mar 21, 2000·Genesis : the Journal of Genetics and Development·C Postic, M A Magnuson
Aug 19, 2000·The American Journal of Gastroenterology·K RyoN Hayashi
Feb 13, 2003·Nature Medicine·Erwei SongJudy Lieberman
May 24, 2003·Journal of Hepatology·Henning Schulze-BergkamenUlrike Protzer
Jun 28, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Konrad L StreetzChristian Trautwein
Dec 12, 2003·Nature·Joseph T OpfermanStanley J Korsmeyer
Mar 5, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Henning Schulze-BergkamenPeter H Krammer
Feb 19, 2005·Science·Joseph T OpfermanStanley J Korsmeyer
Nov 16, 2005·American Journal of Physiology. Gastrointestinal and Liver Physiology·E S Baskin-Bey, G J Gores
Nov 18, 2005·Journal of Hepatology·Wolfgang SieghartVolker Wacheck
Jan 27, 2006·World Journal of Gastroenterology : WJG·Marcus SchuchmannPeter R Galle
Mar 24, 2006·Journal of Hepatology·Henning Schulze-BergkamenPeter R Galle
Jun 27, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Edwina S Baskin-BeyGregory J Gores
Feb 27, 2007·Oncogene·J M Adams, S Cory

❮ Previous
Next ❯

Citations

Sep 8, 2009·The Journal of Biological Chemistry·Howard C MasuokaGregory J Gores
Sep 10, 2013·Inflammatory Bowel Diseases·Martin HausmannGerhard Rogler
Jan 14, 2011·Journal of Gastroenterology and Hepatology·Jorn Markus SchattenbergPeter Robert Galle
Jul 29, 2010·Physiological Reviews·Harmeet MalhiGregory J Gores
Dec 17, 2009·World Journal of Gastroenterology : WJG·Bruno-Christian KoehlerHenning Schulze-Bergkamen
Jan 18, 2014·Cell Death & Disease·K Wang
Mar 5, 2013·Trends in Pharmacological Sciences·Derick HanNeil Kaplowitz
May 13, 2014·Cells·Barbara MojsaSolange Desagher
Jul 22, 2014·Gastroenterology·Tom LueddeRobert F Schwabe
May 29, 2014·Experimental and Toxicologic Pathology : Official Journal of the Gesellschaft Für Toxikologische Pathologie·Kewei Wang
Jan 10, 2014·Journal of Cellular Biochemistry·Wonbaek YooNan Hee Kim
Jun 30, 2012·Biochemistry Research International·Davide Degli EspostiAntoinette Lemoine
Aug 14, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hayato HikitaNorio Hayashi
Sep 30, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sophie C Cazanave, Gregory J Gores
Mar 13, 2013·EMBO Reports·Franziska ErtelGordon C Shore
Feb 18, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Philipp J Jost, Thomas Kaufmann
Oct 20, 2009·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Hayato HikitaNorio Hayashi
Jan 26, 2010·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Achim WeberHenning Schulze-Bergkamen
Jan 5, 2016·Current Pathobiology Reports·Yoon Mee Yang, Ekihiro Seki
Feb 24, 2012·Molecular and Cellular Neurosciences·Craig D MaloneJacqueline L Vanderluit
Dec 15, 2010·Journal of Hepatology·Shih-Yen WengHsin-Fang Yang-Yen
Sep 8, 2010·Biochimica Et Biophysica Acta·Emily F Mason, Jeffrey C Rathmell
Apr 29, 2015·Toxicological Sciences : an Official Journal of the Society of Toxicology·Xiaolong TuJunfeng Zhang
Jun 28, 2011·Journal of Hepatology·Jörn M SchattenbergMarcus Schuchmann
Mar 13, 2012·Free Radical Biology & Medicine·Jörn M SchattenbergMarcus Schuchmann
Aug 2, 2014·European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)·Ru ChenStephen J Beebe
Mar 22, 2015·The American Journal of Pathology·Weina ChenTong Wu
Mar 6, 2015·Cell Death & Disease·V Labi, M Erlacher
Oct 22, 2016·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Sanjoy RoychowdhuryLaura E Nagy
Jul 29, 2016·Journal of Huazhong University of Science and Technology. Medical Sciences = Hua Zhong Ke Ji Da Xue Xue Bao. Yi Xue Ying De Wen Ban = Huazhong Keji Daxue Xuebao. Yixue Yingdewen Ban·Qin YuJu-Sheng Lin
Nov 3, 2016·Leukemia·Y Fernández-MarreroP J Jost

❮ Previous
Next ❯

Related Concepts

Related Feeds

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.

Blood And Marrow Transplantation

The use of hematopoietic stem cell transplantation or blood and marrow transplantation (bmt) is on the increase worldwide. BMT is used to replace damaged or destroyed bone marrow with healthy bone marrow stem cells. Here is the latest research on bone and marrow transplantation.

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis