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SHR Neuro Cancer Cardio Lipid Metab Microb

Strnad, P; Zatloukal, K; Stumptner, C; Kulaksiz, H; Denk, H.
Mallory-Denk-bodies: lessons from keratin-containing hepatic inclusion bodies.
Biochim Biophys Acta. 2008; 1782(12): 764-774. Doi: 10.1016/j.bbadis.2008.08.008 [OPEN ACCESS]
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Leading authors Med Uni Graz

Denk Helmut

Co-authors Med Uni Graz

Stumptner Cornelia

Zatloukal Kurt

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Abstract:

Inclusion bodies are characteristic morphological features of various neuronal, muscular and other human disorders. They share common molecular constituents such as p62, chaperones and proteasome subunits. The proteins within aggregates are misfolded with increased beta-sheet structure, they are heavily phosphorylated, ubiquitinylated and partially degraded. Furthermore, involvement of proteasomal system represents a common feature of virtually all inclusions. Multiple aggregates contain intermediate filament proteins as their major constituents. Among them, Mallory-Denk bodies (MDBs) are the best studied. MDBs represent hepatic inclusions observed in diverse chronic liver diseases such as alcoholic and non-alcoholic steatohepatitis, chronic cholestasis, metabolic disorders and hepatocellular neoplasms. MDBs are induced in mice fed griseofulvin or 3,5-diethoxycarbonyl-1,4-dihydrocollidine and resolve after discontinuation of toxin administration. The availability of a drug-induced model makes MDBs a unique tool for studying inclusion formation. Our review summarizes the recent advances gained from this model and shows how they relate to observations in other aggregates. The MDB formation-underlying mechanisms include protein misfolding, chaperone alterations, disproportional protein expression with keratin 8>keratin 18 levels and subsequent keratin 8 crosslinking via transglutaminase. p62 presence is crucial for MDB formation. Proteasome inhibitors precipitate MDB formation, whereas stimulation of autophagy with rapamycin attenuates their formation.

Find related publications in this database (using NLM MeSH Indexing)

Animals -

Humans -

Inclusion Bodies - metabolism Inclusion Bodies - pathology

Keratins - metabolism

Liver Diseases - metabolism Liver Diseases - pathology

Proteasome Endopeptidase Complex - metabolism

Find related publications in this database (Keywords)

Keratin

Mallory-Denk body

Aggregate

Inclusion

Variant

P62

Ubiquitin

Oxidative stress

Steatohepatitis

Intracellular hyaline body

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