The cytoskeleton in nonalcoholic steatohepatitis: 100 years old but still youthful

Expert Review of Gastroenterology and Hepatology

Volumn 5, Issue 2, 2011, Pages 167-177

  Molnar, Agnes ^a   Haybaeck, Johannes ^b   Lackner, Carolin ^b   Strnad, Pavel ^a  

^a UNIVERSITY HOSPITAL ULM   (Germany)

^b MEDICAL UNIVERSITY OF GRAZ   (Austria)

Author keywords

actin; aggregate; DDC; inclusion; keratin; Mallory Denk body; NASH; p62; tubulin; ubiquitin

Indexed keywords

ACTIN RELATED PROTEIN; ALPHA ACTIN; ALPHA TUBULIN; BETA ACTIN; BETA TUBULIN; COFILIN; CYTOKERATIN 18; CYTOKERATIN 8; DYNEIN ADENOSINE TRIPHOSPHATASE; F ACTIN; TRANSMEMBRANE CONDUCTANCE REGULATOR; VASODILATOR STIMULATED PHOSPHOPROTEIN; WISKOTT ALDRICH SYNDROME PROTEIN;

CYTOSKELETON; DISEASE SEVERITY; HUMAN; INTERMEDIATE FILAMENT; MALLORY BODY; MICROFILAMENT; MICROTUBULE; MICROTUBULE ORGANIZING CENTER; NONALCOHOLIC FATTY LIVER; NONHUMAN; OXIDATIVE STRESS; POLYMERIZATION; PROTEIN FUNCTION; REVIEW; SEROLOGY;

ANIMALS; CYTOSKELETON; FATTY LIVER; FEMALE; HUMANS; INCLUSION BODIES; KERATINS; MALE; MICE; MICROFILAMENT PROTEINS; MICROTUBULE PROTEINS; PROTEINS;

EID: 79954488395     PISSN: 17474124     EISSN: None     Source Type: Journal    
DOI: 10.1586/egh.11.5     Document Type: Review

References (122)

1. Jou J, Choi SS, Diehl AM. Mechanisms of disease progression in nonalcoholic fatty liver disease. Semin. Liver Dis. 28(4), 370-379 (2008).
2. Neuschwander-Tetri BA. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the central role of nontriglyceride fatty acid metabolites. Hepatology 52(2), 774-788 (2010).
3. Ku NO, Strnad P, Zhong BH, Tao GZ, Omary MB. Keratins let liver live: Mutations predispose to liver disease and crosslinking generates Mallory-Denk bodies. Hepatology 46(5), 1639-1649 (2007). (Pubitemid 350155545)
4. Boström P, Rutberg M, Ericsson J et al. Cytosolic lipid droplets increase in size by microtubule-dependent complex formation. Arterioscler. Thromb. Vasc. Biol. 25(9), 1945-1951 (2005). (Pubitemid 41243467)
5. Andersson L, Boström P, Ericson J et al. PLD1 and ERK2 regulate cytosolic lipid droplet formation. J. Cell Sci. 119(Pt 11), 2246-2257 (2006). (Pubitemid 43960314)
6. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P. The cytoskeleton. In: Molecular Biology of the Cell: The Cytoskeleton (4th Edition). Garland Science, NY, USA, 907-982 (2002).
7. Rungger-Brändle E, Gabbiani G. The role of cytoskelet al and cytocontractile elements in pathologic processes. Am. J. Pathol. (3), 361-392 (1983).
8. Mège RM, Gavard J, Lambert M. Regulation of cell-cell junctions by the cytoskeleton. Curr. Opin. Cell Biol. 18(5), 541-548 (2006). (Pubitemid 44349065)
9. Pollard TD, Cooper JA. Actin, a central player in cell shape and movement. Science 326(5957), 1208-1212 (2009).
10. Etienne-Manneville S. From signaling pathways to microtubule dynamics: the key players. Curr. Opin. Cell Biol. 22(1), 104-111 (2010).
11. Godsel LM, Hobbs RP, Green KJ. Intermediate flament assembly: dynamics to disease. Trends Cell Biol. 18(1), 28-37 (2008).
12. Li R, Gundersen GG. Beyond polymer polarity: how the cytoskeleton builds a polarized cell. Nat Rev. Mol. Cell Biol. 9(11), 860-873 (2008).
13. Pollard TD, Borisy GG. Cellular motility driven by assembly and disassembly of actin flaments. Cell 112(4), 453-465 (2003). (Pubitemid 36263079)
14. Bugyi B, Carlier MF. Control of actin flament treadmilling in cell motility Annu. Rev. Biophys. 39, 449-470 (2010).
15. Carlsson AE. Actin dynamics: from nanoscale to microscale. Annu. Rev. Biophys. 39, 91-110 (2010).
16. Ibarra N, Pollitt A, Insall RH. Regulation of actin assembly by SCAR/WAVE proteins. Biochem. Soc Trans. 33, 1243-1246 (2005) (Pubitemid 41779657)
17. Ol azabal IM, Machesky LM. Abp1p and cortactin, new 'hand-holds' for actin. J. Cell Biol. 154(4), 679-682 (2001).
18. Bear JE, Gertler FB. Ena/VASP: towards resolving a pointed controversy at the barbed end. J. Cell Sci. 122, 1947-1953 (2009).
19. Van Troys M, Huyck L, Leyman S, Dhaese S, Vandekerkhove J, Ampe C. Ins and outs of ADF/coflin activity and regulation. Eur. J. Cell Biol. 87(8-9), 649-667 (2008).
20. Andrianantoandro E, Pollard TD. Mechanism of actin flament turnover by severing and nucleation at different concentrations of ADF/coflin. Mol. Cell. 24(1), 13-23 (2006). (Pubitemid 44466682)
21. Bernstein BW, Bamburg JR. ADF/coflin: a functional node in cell biology Trends Cell Biol. 20(4), 187-195 (2010).
22. Quintero-Monzon O, Jonasson EM, Bertling E et al. Reconstitution and dissection of the 600-kDa Srv2/CAP complex: roles for oligomerization and coflin-actin binding in driving actin turnover. J. Biol. Chem. 284(16), 10923-10934 (2009).
23. Kueh HY, Charras GT, Mitchison TJ, Brieher WM. Actin disassembly by coflin, coronin, and Aip1 occurs in bursts and is inhibited by barbed-end cappers. J. Cell Biol. 182(2), 341-353 (2008).
24. Gandhi M, Achard V, Blanchoin L, Goode BL. Coronin switches roles in actin disassembly depending on the nucleotide state of actin. Mol. Cell. 34(3), 364-374 (2009).
25. Arterburn LM, Zurlo J, Yager JD, Overton RM, Heifetz AH. A morphological study of differentiated hepatocytes in vitro. Hepatology 22(1), 175-187 (1995).
26. Novikoff PM, Cammer M, Tao L et al. Three-dimensional organization of rat hepatocyte cytoskeleton: relation to the asialoglycoprotein endocytosis pathway. J. Cell Sci. 109, 21-32 (1996). (Pubitemid 26037924)
27. Tsukada N, Ackerley CA, Phillips MJ. The structure and organization of the bile canalicular cytoskeleton with special reference to actin and actin-binding proteins. Hepatology 21(4), 1106-1113 (1995).
28. Nichols MT, Gidey E, Matzakos T et al. Secretion of cytokines and growth factors into autosomal dominant polycystic kidney disease liver cyst fuid. Hepatology 40(4), 836-846 (2004). (Pubitemid 39288116)
29. Kikuchi S, Hata M, Fukumoto K. Radixin defciency causes conjugated hyperbilirubinemia with loss of Mrp2 from bile canalicular membranes. Nat Genet. 31(3), 320-325 (2002).
30. Sato N, Funayama N, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S. A gene family consisting of ezrin, radixin and moesin. Its specifc localization at actin flament/plasma membrane association sites. J. Cell Sci. 103, 131-143 (1992).
31. Huang JD, Brady ST, Richards BW et al. Direct interaction of microtubule-and actin-based transport motors. Nature 397(6716), 267-270 (1999).
32. Muallem S, Kwiatkowska K, Xu X, Yin HL. Actin flament disassembly is a suffcient fnal trigger for exocytosis in nonexcitable cells. J. Cell Biol. 128(4), 589-598 (1995).
33. Kawahara H, French SW. Role of cytoskeleton in canalicular contraction in cultured differentiated hepatocytes. Am. J. Pathol. 136(3), 521-532 (1990). (Pubitemid 20105919)
34. Tsukada N, Phillips MJ. Bile canalicular contraction is coincident with reorganization of pericanalicular flaments and co-localization of actin and myosin-II. J. Histochem. Cytochem. 41(3), 353-363 (1993). (Pubitemid 23061921)
35. Wakabayashi Y, Lippincott-Schwartz J, Arias IM. Intracellular traffcking of bile salt export pump (ABCB11) in polarized hepatic cells: constitutive cycling between the canalicular membrane and rab11-positive endosomes. Mol. Biol. Cell 15(7), 3485-3496 (2004). (Pubitemid 38850139)
36. Nogales E. Structural insights into microtubule function. Annu. Rev. Biochem. 69, 277-302 (2000).
37. Hawkins T, Mirigian M, Selcuk Yasar M, Ross JL. Mechanics of microtubules. J. Biomech. 43(1), 23-30 (2010).
38. Raynaud-Messina B, Merdes A. y-tubulin complexes and microtubule organization. Curr. Opin. Cell Biol. 19(1), 24-30 (2007). (Pubitemid 46123974)
39. Holmfeldt P, Sellin ME, Gullberg M. Predominant regulators of tubulin monomer-polymer partitioning and their implication for cell polarization. Cell Mol. Life Sci. 66(20), 3263-3276 (2009).
40. Roll-Mecak A, McNally FJ. Microtubule-severing enzymes. Curr. Opin. Cell Biol. 22(1), 96-103 (2010).
41. Galjart N. Plus-end-tracking proteins and their interactions at microtubule ends. Curr. Biol. 20(12), R528-R537 (2010).
42. Gennerich A, Vale RD. Walking the walk: how kinesin and dynein coordinate their steps. Curr. Opin. Cell Biol. 21(1), 59-67 (2009).
43. Hirokawa N, Noda Y, Tanaka Y, Niwa S. Kinesin superfamily motor proteins and intracellular transport. Nat Rev. Mol. Cell Biol. 10(10), 682-696 (2009).
44. Ikegami K, Setou M. Unique post-translational modifcations in specialized microtubule architecture. Cell Struct Funct 35(1), 15-22 (2010).
45. Novikoff PM, Cammer M, Tao L et al. Three-dimensional organization of rat hepatocyte cytoskeleton: relation to the asialoglycoprotein endocytosis pathway J. Cell Sci. 109, 21-32 (1996). (Pubitemid 26037924)
46. Hamm-Alvarez SF, Sheetz MP. Microtubule-dependent vesicle transport: modulation of channel and transporter activity in liver and kidney Physiol. Rev. 78(4), 1109-1129 (1998). (Pubitemid 28491950)
47. Poüs C, Chabin K, Drechou A. Functional specialization of stable and dynamic microtubules in protein traffc in WIF-B cells. J. Cell Biol. 142(1), 153-165 (1998). (Pubitemid 28341147)
48. Phung-Koskas T, Pilon A, Poüs C et al. STAT5B-mediated growth hormone signaling is organized by highly dynamic microtubules in hepatic cells. J. Biol. Chem. 280(2), 1123-1131 (2005).
49. Akner G, Wikström AC, Gustafsson JA. Subcellular distribution of the glucocorticoid receptor and evidence for its association with microtubules. J. Steroid Biochem. Mol. Biol. 52(1), 1-16 (1995).
50. Cohen D, Brennwald PJ, Rodriguez-Boulan E, Müsch A. Mammalian PAR-1 determines epithelial lumen polarity by organizing the microtubule cytoskeleton. J. Cell Biol. 164(5), 717-727 (2004). (Pubitemid 38282955)
51. Godsel LM, Hobbs RP, Green KJ. Intermediate flament assembly: dynamics to disease. Trends Cell Biol. 18(1), 28-37 (2008).
52. Omary MB, Ku NO, Strnad P, Hanada S. Toward unraveling the complexity of simple epithelial keratins in human disease. J. Clin. Invest. 119(7), 1794-1805 (2009).
53. Windoffer R, Kölsch A, Wöll S, Leube RE. Focal adhesions are hotspots for keratin flament precursor formation. J. Cell Biol. 173(3), 341-348 (2006).
54. Kölsch A, Windoffer R, Würfinger T, Aach T, Leube RE. The keratin-flament cycle of assembly and disassembly. J. Cell Sci. 123(Pt 13), 2266-2272 (2010).
55. Kölsch A, Windoffer R, Leube RE. Actin-dependent dynamics of keratin flament precursors. Cell Motil. Cytoskeleton 66(11), 976-985 (2009).
56. Jackson BW, Grund C, Schmid E, Bürki K, Franke WW, Illmensee K. Formation of cytoskelet al elements during mouse embryogenesis. Intermediate flaments of the cytokeratin type and desmosomes in preimplantation embryos. Differentiation 17(3), 161-179 (1980). (Pubitemid 11182897)
57. Loranger A, Gilbert S, Brouard JS, Magin TM, Marceau N. Keratin 8 modulation of desmoplakin deposition at desmosomes in hepatocytes. Exp. Cell Res. 312(20), 4108-4119 (2006). (Pubitemid 44828054)
58. Omary MB, Ku NO, Liao J, Price D. Keratin modifcations and solubility properties in epithelial cells and in vitro. Subcell. Biochem. 31, 105-140 (1998).
59. Toivola DM, Tao GZ, Habtezion A, Liao J, Omary MB. Cellular integrity plus: organelle-related and protein-targeting functions of intermediate flaments. Trends Cell Biol. 15(11), 608-617 (2005). (Pubitemid 41619425)
60. Omary MB, Ku NO, Tao GZ, Toivola DM, Liao J. 'Heads and tails' of intermediate flament phosphorylation: multiple sites and functional insights. Trends Biochem. Sci. 31(7), 383-394 (2006). (Pubitemid 44038919)
61. Snider NT, Weerasinghe SV, Herrmann H, Omary MB. Keratin hypersumoylation alters flament dynamics and is a marker for human liver disease and keratin mutation. J. Biol. Chem. 286(3), 2273-2284 (2011).
62. Van Eyken P, Desmet VJ. Cytokeratins and the liver. Liver 13(3), 113-122 (1993). (Pubitemid 23228705)
63. Zhong B, Strnad P, Selmi C et al. Keratin variants are overrepresented in primary biliary cirrhosis and associate with disease severity Hepatology 50(2), 546-554 (2009).
64. Strnad P, Zhou Q, Hanada S et al. Keratin variants predispose to acute liver failure and adverse outcome: race and ethnic associations. Gastroenterology 139(3), 828-835 (2010).
65. Fickert P, Trauner M, Fuchsbichler A, Stumptner C, Zatloukal K, Denk H. Mallory body formation in primary biliary cirrhosis is associated with increased amounts and abnormal phosphorylation and ubiquitination of cytokeratins. J. Hepatol. 38(4), 387-394 (2003). (Pubitemid 36399238)
66. Toivola DM, Ku NO, Resurreccion EZ, Nelson DR, Wright TL, Omary MB. Keratin 8 and 18 hyperphosphorylation is a marker of progression of human liver disease. Hepatology 40(2), 459-466 (2004). (Pubitemid 39062864)
67. Shi X, van Mierlo JT, French A, Elliott RM. Visualizing the replication cycle of bunyamwera orthobunyavirus expressing fuorescent protein-tagged Gc glycoprotein. J. Virol. 84(17), 8460-8469 (2010).
68. Toivola DM, Strnad P, Habtezion A, Omary MB. Intermediate flaments take the heat as stress proteins. Trends Cell Biol. 20(2), 79-91 (2010).
69. Caulín C, Salvesen GS, Oshima RG. Caspase cleavage of keratin 18 and reorganization of intermediate flaments during epithelial cell apoptosis. J. Cell Biol. 138(6), 1379-1394 (1997). (Pubitemid 27415063)
70. Adams LA, Feldstein AE. Nonalcoholic steatohepatitis: risk factors and diagnosis. Expert Rev. Gastroenterol. Hepatol. 4(5), 623-635 (2010).
71. Shepard BD, Tuma PL. Alcohol-induced alterations of the hepatocyte cytoskeleton. World J. Gastroenterol. 16(11), 1358-1365 (2010).
72. Caron JM. Alteration of microtubule physiology in hepatocytes by insulin. J. Cell Physiol. 138(3), 603-610 (1989). (Pubitemid 19083779)
73. Bugianesi E, Moscatiello S, Ciaravella MF, Marchesini G. Insulin resistance in nonalcoholic fatty liver disease. Curr. Pharm. Des. 16(17), 1941-1951 (2010).
74. Lickteig AJ, Fisher CD, Augustine LM et al. Effux transporter expression and acetaminophen metabolite excretion are altered in rodent models of nonalcoholic fatty liver disease. Drug Metab. Dispos. 35(10), 1970-1978 (2007). (Pubitemid 47481594)
75. Fisher CD, Lickteig AJ, Augustine LM et al. Experimental non-alcoholic fatty liver disease results in decreased hepatic uptake transporter expression and function in rats. Eur. J. Pharmacol. 613(1-3), 119-127 (2009).
76. Strnad P, Stumptner C, Zatloukal K, Denk H. Intermediate flament cytoskeleton of the liver in health and disease. Histochem. Cell Biol. 129(6), 735-749 (2008).
77. Linder S. Cytokeratin markers come of age. Tumour Biol. 28(4), 189-195 (2007). (Pubitemid 47379291)
78. Yilmaz Y, Kedrah AE, Ozdogan O. Cytokeratin-18 fragments and biomarkers of the metabolic syndrome in nonalcoholic steatohepatitis. World J. Gastroenterol. 15(35), 4387-4391 (2009).
79. Leers MP, Kölgen W, Björklund V et al. Immunocytochemical detection and mapping of a cytokeratin 18 neo-epitope exposed during early apoptosis. J. Pathol. (5), 567-572 (1999). (Pubitemid 29151999)
80. Marra F, Gastaldelli A, Svegliati Baroni G, Tell G, Tiribelli C Molecular basis and mechanisms of progression of non-alcoholic steatohepatitis. Trends Mol. Med. 14(2), 72-81 (2008).
81. Yilmaz Y, Ulukaya E, Dolar E. Serum M30 levels: a potential biomarker of severe liver disease in nonalcoholic fatty liver disease and normal aminotransferase levels. Hepatology 49 (2), 697; author reply 697 (2009).
82. Vos MB, Barve S, Joshi-Barve S, Carew JD, Whitington PF, McClain CJ. Cytokeratin 18, a marker of cell death, is increased in children with suspected nonalcoholic fatty liver disease. J. Pediatr. Gastroenterol. Nutr. 47(4), 481-485 (2008).
83. Emanuele E. Is biopsy always necessary? Toward a clinico-laboratory approach for diagnosing nonalcoholic steatohepatitis in obesity Hepatology 48(6), 2086-2087; author reply 2087 (2008).
84. Malik R, Chang M, Bhaskar K et al. The clinical utility of biomarkers and the nonalcoholic steatohepatitis CRN liver biopsy scoring system in patients with nonalcoholic fatty liver disease. J. Gastroenterol. Hepatol. 24(4), 564-568 (2009).
85. Feldstein A, Kleiner D, Kravetz D, Buck M. Severe hepatocellular injury with apoptosis induced by a hepatitis C polymerase inhibitor. J. Clin. Gastroenterol. 43(4), 374-381 (2009).
86. Wieckowska A, Zein NN, Yerian LM, Lopez AR, McCullough AJ, Feldstein AE. In vivo assessment of liver cell apoptosis as a novel biomarker of disease severity in nonalcoholic fatty liver disease. Hepatology 44(1), 27-33 (2006). (Pubitemid 44049136)
87. Feldstein AE, Wieckowska A, Lopez AR, Liu YC, Zein NN, McCullough AJ. Cytokeratin-18 fragment levels as noninvasive biomarkers for nonalcoholic steatohepatitis: a multicenter validation study. Hepatology 50(4), 1072-1078 (2009).
88. Tao GZ, Li DH, Zhou Q et al. Monitoring of epithelial cell caspase activation via detection of durable keratin fragment formation. J. Pathol. 215(2), 164-174 (2008). (Pubitemid 351786035)
89. Mallory FB. Cirrhosis of the liver. Five different types of lesions from which it may arise. Bull. Johns Hopkins Hosp. 22, 69-75 (1911).
90. Jensen K, Gluud C. The Mallory body: morphological, clinical and experimental studies (part 1 of a literature survey). Hepatology 20(4 Pt 1), 1061-1077 (1994).
91. Zatloukal K, Stumptner C, Fuchsbichler A et al. The keratin cytoskeleton in liver diseases. J. Pathol. 204(4), 367-376 (2004). (Pubitemid 39468148)
92. Pauline de la M Hall. Alcoholic liver disease. In: MacSween's Pathology of the Liver (Fifth Edition). Burt A, Portmann B, Ferrell L (Eds). Churchill Livingstone Elsevier, PA, USA, 327-365 (2007).
93. Pinto HC, Baptista A, Camilo ME, Valente A, Saragoça A, de Moura MC. Nonalcoholic steatohepatitis. Clinicopathological comparison with alcoholic hepatitis in ambulatory and hospitalized patients. Dig Dis. Sci. 41(1), 172-179 (1996). (Pubitemid 26064854)
94. Zatloukal K, French SW, Stumptner C et al. From Mallory to Mallory-Denk bodies: what, how and why? Exp. Cell Res. 313(10), 2033-2049 (2007). (Pubitemid 46842981)
95. Lefkowitch JH. Morphology of alcoholic liver disease. Clin. Liver Dis. 9(1), 37-53 (2009). (Pubitemid 40341945)
96. Lackner C, Gogg-Kamerer M, Zatloukal K, Stumptner C, Brunt EM, Denk H. Ballooned hepatocytes in steatohepatitis: the value of keratin immunohistochemistry for diagnosis. J. Hepatol. 48(5), 821-828 (2008).
97. Denk H, Stumptner C, Zatloukal K. Mallory bodies revisited. J. Hepatol. 32(4), 689-702 (2000). (Pubitemid 30180391)
98. Sheth SG, Gordon FD, Chopra S. Nonalcoholic steatohepatitis. Ann. Intern. Med. 126(2), 137-145 (1997). (Pubitemid 27058588)
99. Chalasani N, Wilson L, Kleiner DE et al. Relationship of steatosis grade and zonal location to histological features of steatohepatitis in adult patients with non-alcoholic fatty liver disease. J. Hepatol. 48(5), 829-834 (2008).
100. Schwimmer JB, Behling C, Newbury R et al. Histopathology of pediatric nonalcoholic fatty liver disease. Hepatology 42(3), 641-649 (2005). (Pubitemid 41233657)
101. Nobili V, Marcellini M, Devito R et al. NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice. Hepatology 44(2), 458-465 (2006). (Pubitemid 44214885)
102. Ko JS, Yoon JM, Yang HR et al. Clinical and histological features of nonalcoholic fatty liver disease in children. Dig Dis. Sci. (10), 2225-2230 (2009).
103. Denk H, Franke WW, Eckerstorfer R, Schmid E, Kerjaschki D. Formation and involution of Mallory bodies ('alcoholic hyalin') in murine and human liver revealed by immunofuorescence microscopy with antibodies to prekeratin. Proc. Natl Acad. Sci. USA 76(8), 4112-4116 (1979). (Pubitemid 9249034)
104. Hanada S, Strnad P, Brunt EM, Omary MB. The genetic background modulates susceptibility to mouse liver Mallory-Denk body formation and liver injury Hepatology 48(3), 943-952 (2008).
105. Mendler MH, Kanel G, Govindarajan S. Proposal for a histological scoring and grading system for non-alcoholic fatty liver disease. Liver Int. 25(2), 294-304 (2005).
106. Kleiner DE, Brunt EM, Van Natta M et al. Design and validation of a histological scoring system for nonalcoholic fatty liver disease. Hepatology 41(6), 1313-1321 (2005). (Pubitemid 40770284)
107. Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCullough AJ. Nonalcoholic fatty liver disease: a spectrum of clinical and pathological severity. Gastroenterology 116(6), 1413-1419 (1999). (Pubitemid 29258890)
108. Cortez-Pinto H, Baptista A, Camilo ME, De Moura MC. Nonalcoholic steatohepatitis-a long-term follow-up study: comparison with alcoholic hepatitis in ambulatory and hospitalized patients. Dig Dis. Sci. 48(10), 1909-1913 (2003). (Pubitemid 37419951)
109. Caldwell S, Ikura Y, Dias D et al. Hepatocellular ballooning in NASH. J. Hepatol. 53(4), 719-723 (2010).
110. Magin TM, Schröder R, Leitgeb S et al. Lessons from keratin 18 knockout mice: formation of novel keratin flaments, secondary loss of keratin 7 and accumulation of liver-specifc keratin 8-positive aggregates. J. Cell Biol. 140(6), 1441-1451 (1998). (Pubitemid 28152992)
111. Zatloukal K, Stumptner C, Lehner M et al. Cytokeratin 8 protects from hepatotoxicity, and its ratio to cytokeratin 18 determines the ability of hepatocytes to form Mallory bodies. Am. J. Pathol. 156(4), 1263-1274 (2000). (Pubitemid 30660005)
112. Nakamichi I, Toivola DM, Strnad P et al. Keratin 8 overexpression promotes mouse Mallory body formation. J. Cell Biol. 171(6), 931-937 (2005). (Pubitemid 41815825)
113. Harada M, Strnad P, Resurreccion EZ, Ku NO, Omary MB. Keratin 18 overexpression but not phosphorylation or flament organization blocks mouse Mallory body formation. Hepatology 45 (1), 88-96 (2007). (Pubitemid 46144368)
114. Strnad P, Harada M, Siegel M et al. Transglutaminase 2 regulates mallory body inclusion formation and injury-associated liver enlargement. Gastroenterology 132(4), 1515-1526 (2007). (Pubitemid 46627586)
115. Strnad P, Zatloukal K, Stumptner C, Kulaksiz H, Denk H. Mallory-Denk-bodies: lessons from keratin-containing hepatic inclusion bodies. Biochim. Biophys. Acta 1782(12), 764-774 (2008).
116. Strnad P, Tao GZ, So P et al. 'Toxic memory' via chaperone modifcation is a potential mechanism for rapid Mallory-Denk body reinduction. Hepatology 48(3), 931-942 (2008).
117. Harada M, Hanada S, Toivola DM, Ghori N, Omary MB. Autophagy activation by rapamycin eliminates mouse Mallory-Denk bodies and blocks their proteasome inhibitor-mediated formation. Hepatology 47(6), 2026-2035 (2008). (Pubitemid 351945569)
118. Rodriguez-Navarro JA, Cuervo AM. Autophagy and lipids: tightening the knot. Semin. Immunopathol. 32(4), 343-353 (2010).
119. Kachi K, Wong PT, French SW. Molecular structural changes in Mallory body proteins in human and mouse livers: an infrared spectroscopy study Exp. Mol. Pathol. 59(3), 197-210 (1993). (Pubitemid 24126642)
120. Neuschwander-Tetri BA. Hepatic lipotoxicity and the pathogenesis of nonalcoholic steatohepatitis: the central role of nontriglyceride fatty acid metabolites. Hepatology 52(2), 774-788 (2010).
121. Li J, Bardag-Gorce F, Dedes J et al. S-adenosylmethionine prevents Mallory Denk body formation in drug-primed mice by inhibiting the epigenetic memory Hepatology 47(2), 613-624 (2008). (Pubitemid 351280730)
122. Hanada S, Snider NT, Brunt EM, Hollenberg PF, Omary MB. Gender dimorphic formation of mouse Mallory-Denk bodies and the role of xenobiotic metabolism and oxidative stress. Gastroenterology 138(4), 1607-1617 (2010).