Formation and involution of Mallory bodies ("alcoholic hyalin") in murine and human liver revealed by immunofluorescence microscopy with antibodies to prekeratin.

Denk, Helmut; Franke, Werner W.; Eckerstorfer, R.; Schmid, Erika Nardon; Kerjaschki, Dontscho

doi:10.1073/pnas.76.8.4112

Cited by 104 publications

(39 citation statements)

References 11 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, MDBs have also been observed at the cell periphery, associated in distinct cases with keratin IFs or desmosomes (21). These different locations were correlated to stages of MDB formation in the griseofulvin-fed mouse model; in this model, smaller, globular aggresomes reflect early formation of MDBs, whereas in later stages of formation, the MDBs become larger, perinuclear structures (22). Aggresomes are also observed in renal cell carcinoma (23), nonneoplastic pancreatic cells (24), and patients with interstitial pneumonitis (25), as well as in the cytoplasm of especially swollen alveolar epithelial cells.…”

Section: Keratin Ifs and Aggresomesmentioning

confidence: 91%

The Role of the Ubiquitin Proteasome Pathway in Keratin Intermediate Filament Protein Degradation

Rogel

Jaitovich²,

Ridge

2010

Proceedings of the American Thoracic Society

View full text Add to dashboard Cite

Section: Keratin Ifs and Aggresomesmentioning

confidence: 91%

The Role of the Ubiquitin Proteasome Pathway in Keratin Intermediate Filament Protein Degradation

Rogel

Jaitovich²,

Ridge

2010

Proceedings of the American Thoracic Society

View full text Add to dashboard Cite

“…This suggests that additional removal of 6 amino acids may cause conformational changes that prevent COU-1 from binding. Finally, changes in the K8/K18 heterotypic network have been observed in Mallory bodies, which are characteristic cytoplasmic inclusions in hepatocytes associated with alcoholic hepatitis and other chronic hepatocellular injuries including cholestasis and various metabolic disturbances (55)(56)(57). The Mallory bodies consist predominantly of K8 and variable amounts of K18 assembled in a nonfilamentous manner as well as nonkeratin components, such as the M M 120-1 antigen and ubiquitin.…”

Section: Discussionmentioning

confidence: 99%

Cancer-associated Cleavage of Cytokeratin 8/18 Heterotypic Complexes Exposes a Neoepitope in Human Adenocarcinomas

Ditzel¹,

Strik²,

Kobæk-Larsen³

et al. 2002

Journal of Biological Chemistry

View full text Add to dashboard Cite

The intermediate filament network in simple glandular epithelial cells predominantly consists of heterotypic complexes of cytokeratin 8 (K8) and cytokeratin 18 (K18). In contrast to other cytokeratins, K8 and K18 are persistently expressed during malignant transformation, but changes in cell morphology are accompanied by alterations in the intermediate filament network. To study molecular changes, K8 and K18 were purified from surgically removed colon cancer and normal epithelia tissues. Western blotting and amino acid sequencing revealed the presence of abundant K8 and K18 fragments, truncated at the N terminus, from cancerous, but not normal, epithelial cells. The fragmentation pattern indicates proteolysis mediated by several enzymes, including trypsin-like enzymes. The cancer-associated forms of K8 and K18 are specifically recognized by the human antibody, COU-1, cloned from the B cells of a cancer patient. We demonstrate that COU-1 recognizes a unique conformational epitope presented only by a complex between K8 and K18. The epitope is revealed after proteolytic removal of the head domain of either K8 or K18. A large panel of recombinant K8 and K18 fragments, deleted N-or C-terminally, allowed for the localization of the COU-1 epitope to the N-terminal part of the rod domains. Using surface plasmon resonance, the affinity of COU-1 for this epitope was determined to be 10 9 M ؊1 , i.e. more than 2 orders of magnitude higher than for intact heterotypic K8/K18 complexes. The cellular distribution of truncated K8/K18 heterotypic complexes in viable adenocarcinomas cells was probed using COU-1 showing small fibrillar structures distinct from those of intact K8/K18 complexes. Previously we demonstrated the binding and subsequent internalization of recombinant Fab COU-1 to live cancer cells. We have thus characterized a cancer neoepitope recognized by the humoral immune system. The results have biological as well as clinical implications.The 10 nm intermediate filaments (IF) 1 provide resilience in response to mechanical stress by forming a stable network attached to specific desmosome cell-cell contacts (1). IF can be classified into groups expressed in higher eukaryotes in a tissue-specific and cell type-restricted pattern (2, 3). In epithelial cells, IFs consist of stoichiometrically equal amounts of type I (smaller and acidic) and type II (larger, neutral, or basic) cytokeratin polypeptides, which form strongly interacting heterodimers (4 -6). Cytokeratin 8 (K8) and cytokeratin 18 (K18), type I and II, respectively, are the major components of IFs of simple or single layer epithelia, such as those of the intestine, the liver, and the breast ducts, although cytokeratin 19 (K19) is also present and forms heterodimers with K8 (2, 5). The assembly of IF involves several association steps where the ␣-helical rod domain of the cytokeratin molecules plays the central role (7-9). The head and the tail domains are not thought to be part of the filamentous backbone but to protrude laterally and contribute to profilame...

show abstract

“…7,9,11,15,20,23 Nonviral inclusions characterized as amorphous intracytoplasmic eosinophilic hyaline bodies have been demonstrated in human and animal tissues afflicted with a diverse array of disease conditions, including alcoholism, neoplasia, morbid obesity, Indian childhood cirrhosis, pyrrolizidine alkaloid and copper exposure, and prolonged griseofulvin treatment. 2,[7][8][9]11,15,26 These inclusion bodies represent intracytoplasmic aggregates of various intermediate filaments, including cytokeratins, vimentin, and neurofilaments. 8,10,11,20 In some cases, the intermediate filaments within nonmembrane-bound inclusions were thickened by a diffuse coating of ubiqutin.…”

mentioning

confidence: 99%

“…26 Because of the morphologic and histochemical similarities between IBD inclusions and other types of nonviral intracytoplasmic bodies, we decided to study and better characterize the IBD virus (IBDV)-associated inclusions. 2,[7][8][9]11,15,25,26 The objectives of the study were to examine the relationship between the retrovirus-like agent and its associated nonviral inclusion bodies and to identify and characterize the material within the inclusion bodies.…”

mentioning

confidence: 99%

Isolation and Characterization of an Antigenically Distinct 68- kd Protein from Nonviral Intracytoplasmic Inclusions in Boa Constrictors Chronically Infected with the Inclusion Body Disease Virus (IBDV: Retroviridae)

et al. 2000

View full text Add to dashboard Cite

Abstract.The relationship between a retroviral infection and the development of nonviral intracytoplasmic inclusion bodies was studied in a Boa constrictor model. Twelve juvenile age-and size-matched inclusion body disease (IBD)-negative boas were randomly divided into three groups. Each group was inoculated intraperitoneally with 1 ml of an IBD virus (IBDV)-infected liver homogenate or 1 ml of normal boa liver homogenate (sham-inoculated control) or was left untreated. All boas were monitored for development of IBD by daily examination and serial liver biopsy over 1 year. The 4 IBDV-inoculated boas became IBDV and inclusion positive by 10 weeks postinoculation. The average size and density of inclusion bodies increased with the duration of infection. Ultrastructurally, inclusion bodies Ͻ2 m in diameter consisted of intracytoplasmic aggregates of granular electron-dense material that were not membrane limited. Larger inclusions (3-6 m in diameter) were characterized as membrane-bound aggregates of amorphous to granular electron-dense material admixed with membranelike fragments. The sham-inoculated and untreated control snakes did not become inclusion or IBDV positive. Direct comparison of the protein electrophoretograms of IBDV-infected and normal boa tissues demonstrated a prominent 68-kd protein band unique to infected inclusion-positive tissues. Monoclonal antibodies directed against the 68-kd protein band specifically labeled inclusion bodies. The results of this study demonstrate that IBD inclusions represent an intracytoplasmic accumulation of an antigenically distinct IBDV-associated protein.

show abstract

Formation and involution of Mallory bodies ("alcoholic hyalin") in murine and human liver revealed by immunofluorescence microscopy with antibodies to prekeratin.

Abstract: Antibodies raised against prekeratin intensely and specifically stain, in immunofluorescence microscopy, Mallory bodies ("alcoholic hyalin")

Cited by 104 publications

References 11 publications

The Role of the Ubiquitin Proteasome Pathway in Keratin Intermediate Filament Protein Degradation

The Role of the Ubiquitin Proteasome Pathway in Keratin Intermediate Filament Protein Degradation

Cancer-associated Cleavage of Cytokeratin 8/18 Heterotypic Complexes Exposes a Neoepitope in Human Adenocarcinomas

Isolation and Characterization of an Antigenically Distinct 68- kd Protein from Nonviral Intracytoplasmic Inclusions in Boa Constrictors Chronically Infected with the Inclusion Body Disease Virus (IBDV: Retroviridae)

Contact Info

Product

Resources

About