Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Salmhofer, H; Rainer, I; Zatloukal, K; Denk, H.
Posttranslational events involved in griseofulvin-induced keratin cytoskeleton alterations.
Hepatology. 1994; 20(3):731-740
Doi: 10.1016%2F0270-9139%2894%2990111-2
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Denk Helmut
- Zatloukal Kurt
- Altmetrics:
- Dimensions Citations:
- Plum Analytics:
- Scite (citation analytics):
- Abstract:
- Alcoholic hepatitis is a disease associated with profound alterations of the hepatocytic intermediate filament cytoskeleton. Similar cytoskeletal alterations can be induced in mice with prolonged feeding of the fungistatic drug griseofulvin. Murine hepatocytic intermediate filaments are composed of equimolar amounts of keratin polypeptides A (type II) and D (type I). Griseofulvin intoxication of mice leads to diminution, derangement and even loss of the cytoplasmic keratin meshwork and formation of keratin-containing cytoplasmic inclusions, termed Mallory bodies. To study protein alterations leading to disturbance of keratin filament architecture, soluble keratin polypeptides and keratin filaments were purified from griseofulvin-damaged and control mouse livers. In griseofulvin-damaged livers, more acidic isoforms occurred in soluble keratin D, whereas the corresponding filaments had a polypeptide composition similar to that in controls. In vivo [32P]orthophosphate incorporation revealed that the shift of isoelectric forms toward more acidic spots was due to hyperphosphorylation of keratin D. The nature of the kinase(s) involved has yet to be elucidated. In addition, rapid proteolysis only of soluble keratin A was detected in vitro, and there is evidence for increased proteolysis in griseofulvin damage in vivo. The enzyme involved has features of a calpain-type protease. Posttranslational modifications play a substantial role in the disturbance of keratin intermediate filament homeostasis in vivo.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Cytoskeleton - drug effects
- Endopeptidases - metabolism
- Griseofulvin - pharmacology
- Intermediate Filaments - metabolism
- Intracellular Membranes - metabolism
- Keratins - metabolism
- Liver - drug effects
- Male - drug effects
- Mice - drug effects
- Mice, Inbred Strains - drug effects
- Peptide Hydrolases - metabolism
- Peptides - metabolism
- Phosphorylation - metabolism
- Polymers - metabolism
- Protein Processing, Post-Translational - metabolism
- Solubility - metabolism