Novel insights into changes in biochemical properties of keratins 8 and 18 in griseofulvin-induced toxic liver injury

Experimental and Molecular Pathology
Anne-Marie FortierMonique Cadrin

Abstract

Keratins 8 and 18 (K8/18) intermediate filament proteins are believed to play an essential role in the protection of hepatocytes against mechanical and toxic stress. This assertion is mainly based on increased hepatocyte fragility observed in transgenic mice deficient in K8/18, or carrying mutations on K8/18. The molecular mechanism by which keratins accomplish their protective functions has not been totally elucidated. Liver diseases such as alcoholic hepatitis and copper metabolism diseases are associated with modifications, in hepatocytes, of intermediate filament organisation and the formation of K8/18 containing aggregates named Mallory-Denk bodies. Treatment of mice with a diet containing griseofulvin induces the formation of Mallory-Denk bodies in hepatocytes. This provides a reliable animal model for assessing the molecular mechanism by which keratins accomplish their protective role in the response of hepatocytes to chemical injuries. In this study, we found that griseofulvin intoxication induced changes in keratin solubility and that there was a 5% to 25% increase in the relative amounts of soluble keratin. Keratin phosphorylation on specific sites (K8 pS79, K8 pS436 and K18 pS33) was increased and prominent in the in...Continue Reading

References

Nov 1, 1994·Trends in Biochemical Sciences·E G Krebs
Jan 1, 1994·Annual Review of Biochemistry·E Fuchs, K Weber
Jan 31, 1998·The Journal of Biological Chemistry·N O KuM B Omary
Nov 26, 1998·Experimental and Molecular Pathology·Q X YuanS W French
May 24, 2001·The New England Journal of Medicine·N O KuM B Omary
Jan 10, 2002·The Journal of Biological Chemistry·Tao HeJohn E Eriksson
Jan 17, 2002·Current Opinion in Cell Biology·Pierre A Coulombe, M Bishr Omary
Mar 28, 2002·Proceedings of the National Academy of Sciences of the United States of America·Nam-On KuM Bishr Omary
Sep 17, 2002·Experimental and Molecular Pathology·Fawzia Bardag-GorceSamuel William French
Mar 19, 2003·International Review of Cytology·Harald HerrmannThomas M Magin
Apr 30, 2003·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Nam-On KuM Bishr Omary
May 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Nam-On KuM Bishr Omary
Jun 15, 2004·Experimental Cell Research·Bert SchutteFrans C S Ramaekers
Sep 16, 2004·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Diana M ToivolaM Bishr Omary
Feb 24, 2005·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Qin ZhouM Bishr Omary
Mar 28, 2006·Experimental and Molecular Pathology·Li NanSamuel W French
Apr 13, 2006·The Journal of Biological Chemistry·Qin ZhouM Bishr Omary
May 27, 2006·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Pavel StrnadM Bishr Omary
Jun 20, 2006·Trends in Biochemical Sciences·M Bishr OmaryJian Liao
Jul 5, 2006·The Journal of Cell Biology·Nam-On Ku, M Bishr Omary
May 29, 2007·Experimental Cell Research·Kurt ZatloukalM Bishr Omary
May 31, 2007·The Journal of Cell Biology·Stefan WöllRudolf E Leube
Oct 30, 2007·Experimental and Molecular Pathology·Fataneh AmidiSamuel W French
Dec 7, 2007·Current Biology : CB·Alexei MikhailovConly L Rieder
Jan 18, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sivaraj SivaramakrishnanKaren M Ridge
Jan 23, 2009·International Journal of Biological Sciences·Tina M Thornton, Mercedes Rincon

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Citations

Sep 7, 2011·The Journal of Cell Biology·Reinhard WindofferRudolf E Leube
Sep 20, 2011·Clinica Chimica Acta; International Journal of Clinical Chemistry·Yusuf Yilmaz
Apr 12, 2011·Expert Review of Gastroenterology & Hepatology·Mariana Verdelho Machado, Helena Cortez-Pinto

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