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In vitro production of Mallory bodies and intracellular hyaline bodies: The central role of sequestosome 1 by Conny Stumptner; Andrea Fuchsbichler; Kurt Zatloukal; Helmut Denk is a Medicine article available to read on EtoBox.

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Mallory bodies (MBs) and intracellular hyaline bodies (IHBs) are characteristic hepatocellular inclusions. MBs are hallmarks of steatohepatitis, whereas IHBs have first been detected in hepatocellular carcinoma. MBs and IHBs contain ubiquitin and sequestosome 1 / p62 (p62), a stress-inducible adapter protein with affinity to polyubiquitinated proteins. MBs differ from IHBs by their keratin content and morphology. In vitro transfections were undertaken to study under defined conditions MB and IHB formation, their pathogenesis, and relationship. CHO-K1, TIB73, and HeLa cells were transfected with keratin 8, keratin 18, ubiquitin, p62, and p62 lacking the ubiquitin binding domain (p62⌬UBA) and analyzed by immunofluorescence, immunoelectron microscopy, and immunoblotting. Transfection of p62 complementary deoxyribonucleic acid (cDNA) alone led to cytoplasmic aggregates consisting of filaments mostly arranged in parallel arrays resembling amyloid and type 1 MBs. Transfection of p62 and ubiquitin resulted in globular cytoplasmic aggregates with indistinct fibrillar ultrastructure resembling IHBs. Cotransfection of p62, keratin 8, and ubiquitin was necessary to produce in vitro type 2 MBs

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Author

Conny Stumptner; Andrea Fuchsbichler; Kurt Zatloukal; Helmut Denk

Publisher

Ovid Technologies (Wolters Kluwer Health)

Published

2007

Language

EN

Field

Medicine (Health Sciences)