Molecular structural changes in Mallory body proteins in human and mouse livers: an infrared spectroscopy study.
To study the molecular structure of Mallory body (MB) proteins we applied infrared spectroscopy of the isolated MBs from livers obtained from autopsied patients with alcoholic cirrhosis and griseofulvin-fed (GF-fed) mice. Liver frozen sections were extracted with detergent and digested with deoxyribo- and ribonuclease and collagenase. MB-enriched fractions were then separated out using the aqueous two-phase polymer system. Immunohistochemical and electron microscopic examination showed that the MB composition was virtually identical in human and mouse livers. Infrared spectra of both MB samples showed that the MBs had more numerous and stronger intermolecular hydrogen bonding than did the background control fractions as well as the cytoskeletal fraction from control and GF-fed mice. This may explain why the proteins in MBs are aggregated. The relative amount of beta-sheets was increased compared to the alpha-helices in the MBs, indicating that conformational changes in the cytokeratin peptides of the MBs had occurred. This may explain why the antigenic sites observed in MB proteins show changes in affinity for antibodies to cytokeratins as observed by immunohistochemical staining of MBs.
Kachi
K
K
Department of Pathology, Harbor-UCLA Medical Center, Torrance 90509.
Wong
P T
PT
French
S W
SW
D000818:Animals; D056486:Chemical and Drug Induced Liver Injury; D003598:Cytoskeletal Proteins / Q000378:metabolism; D006118:Griseofulvin; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism*; D008099:Liver / Q000378:metabolism* / Q000648:ultrastructure; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism / Q000473:pathology; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D011487:Protein Conformation; D011506:Proteins / Q000378:metabolism*; D013055:Spectrophotometry, Infrared
D003598:Cytoskeletal Proteins; C027596:Mallory body protein, human; C488922:Mallory body protein, mouse; D011506:Proteins; D006118:Griseofulvin