Alteration in molecular structure of cytoskeleton proteins in griseofulvin-treated mouse liver: a pressure tuning infrared spectroscopy study.
Different liver diseases are associated with modifications in hepatocyte cytoskeletal organization and formation of Mallory bodies (MBs). Since the structure of a protein is critical for its function, we studied the changes in the molecular structure of the cytoskeletal protein in the liver from mice fed griseofulvin (GF), which is a good animal model for studying liver disease. Using pressure-tuning infrared spectroscopy we compared the infrared spectra of the cytoskeletal proteins from control liver and griseofulvin treated liver. The results show that the overall structure of the cytoskeletal protein was modified by the griseofulvin treatment. A relative increase in the amount of alpha-helices to beta-sheets was observed in the liver cytoskeleton from the GF-treated mice. Moreover, the random coil and the turn segments were dramatically decreased compared to controls. Pressure-induced modifications including denaturation were irreversible in the control samples whereas they were reversible in the griseofulvin-treated samples. These changes reflect important fundamental modifications in the molecular structure of the cytoskeletal proteins in the griseofulvin-treated hepatocytes. We suggest that these changes are related to the modification of the organization of intermediate filaments and the formation of MBs that occur in the GF-treated liver.
Department of Pathology, Faculty of Health Sciences, University of Ottawa, Ontario, Canada.
M
M
Cadrin
S W
SW
French
P T
PT
Wong
D000818:Animals; D003598:Cytoskeletal Proteins / Q000032:analysis*; D003599:Cytoskeleton / Q000737:chemistry / Q000648:ultrastructure; D004591:Electrophoresis, Polyacrylamide Gel; D006118:Griseofulvin / Q000494:pharmacology*; D008099:Liver / Q000737:chemistry / Q000166:cytology / Q000187:drug effects*; D051379:Mice; D008809:Mice, Inbred C3H; D015394:Molecular Structure; D013055:Spectrophotometry, Infrared
D003598:Cytoskeletal Proteins; D006118:Griseofulvin