Microtubules are required for cytokeratin aggresome (Mallory body) formation in hepatocytes: an in vitro study

• Published in: Experimental and molecular pathology 2003-04, Vol.74 (2), p.173-179
• Main Authors: Riley, N.E, Bardag-Gorce, F, Montgomery, R.O, Li, J, Lungo, W, Lue, Y.H, French, S.W
• Format: Article
• Language: English
• Subjects: Aggresomes; Animals; Antibodies - metabolism; Cells, Cultured; Colchicine - pharmacology; Dihydropyridines - pharmacology; Hepatocytes; Hepatocytes - drug effects; Hepatocytes - metabolism; Hepatocytes - pathology; Hepatocytes - ultrastructure; Inclusion Bodies - chemistry; Inclusion Bodies - metabolism; Inclusion Bodies - pathology; Keratins - metabolism; Liver - drug effects; Liver - metabolism; Liver - pathology; Liver - ultrastructure; Lumicolchicines - pharmacology; Male; Mallory bodies; Mice; Mice, Inbred C3H; Microtubules; Microtubules - drug effects; Microtubules - physiology; Nocodazole - pharmacology; Ubiquitin - metabolism
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/S0014-4800(03)00005-4

Mallory bodies are cytokeratin-ubiquitin aggresomes that form in hepatocytes in many different chronic liver diseases. One of the key components in aggresome formation, not yet investigated in Mallory body formation, is the role of microtubules. An in vitro tissue culture assay is required to test for microtubule involvement in Mallory body formation so that Mallory body formation can be observed in the presence or absence of microtubule-disrupting agents. In this report, a new model of in vitro Mallory body formation was developed, which uses cultured hepatocytes isolated from drug-primed mice. When hepatocytes were incubated in the presence of antimicrotubule agents, they failed to form Mallory bodies. It is concluded that intact microtubules are required for Mallory body formation.