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Titolo:
Hepatocyte cytokeratins are hyperphosphorylated at multiple sites in humanalcoholic hepatitis and in a Mallory body mouse model
Autore:
Stumptner, C; Omary, MB; Fickert, P; Denk, H; Zatloukal, K;
Indirizzi:
Graz Univ, Dept Pathol, Div Expt Cell Res & Oncol, A-8036 Graz, Austria Graz Univ Graz Austria A-8036 xpt Cell Res & Oncol, A-8036 Graz, Austria Graz Univ, Dept Med, A-8036 Graz, Austria Graz Univ Graz Austria A-8036Graz Univ, Dept Med, A-8036 Graz, Austria VA Med Ctr, Dept Med, Palo Alto, CA USA VA Med Ctr Palo Alto CA USAVA Med Ctr, Dept Med, Palo Alto, CA USA Stanford Univ, Palo Alto, CA 94304 USA Stanford Univ Palo Alto CA USA 94304 anford Univ, Palo Alto, CA 94304 USA
Titolo Testata:
AMERICAN JOURNAL OF PATHOLOGY
fascicolo: 1, volume: 156, anno: 2000,
pagine: 77 - 90
SICI:
0002-9440(200001)156:1<77:HCAHAM>2.0.ZU;2-J
Fonte:
ISI
Lingua:
ENG
Soggetto:
KERATIN INTERMEDIATE FILAMENTS; GRISEOFULVIN-TREATED MICE; EPITHELIAL-CELLS; LEWY BODY; PHOSPHORYLATED NEUROFILAMENTS; ALZHEIMERS-DISEASE; CULTURED-CELLS; LIVER-DISEASE; PROTEINS; BODIES;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
64
Recensione:
Indirizzi per estratti:
Indirizzo: Zatloukal, K Graz Univ, Dept Pathol, Div Expt Cell Res & Oncol, Auenbruggerpl 25, A-8036 Graz, Austria Graz Univ Auenbruggerpl 25 Graz Austria A-8036 Graz, Austria
Citazione:
C. Stumptner et al., "Hepatocyte cytokeratins are hyperphosphorylated at multiple sites in humanalcoholic hepatitis and in a Mallory body mouse model", AM J PATH, 156(1), 2000, pp. 77-90

Abstract

Alcoholic hepatitis (AH) is associated with cytokeratin 8 and 18 (CK8/18) accumulation as cytoplasmic inclusion bodies, termed Mallory bodies (MBs). Studies with MB mouse models and cultured hepatocytes suggested that CK8/18hyperphosphorylation might be involved in MB formation, However, no data exist on phosphorylation of CK8/18 in human AR. In this study, antibodies that selectively recognize phosphorylated epitopes of CK8 or CK18 were used to analyze CK8/18 phosphorylation states in normal human and murine livers, human AH biopsies, and livers of 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC)-intoxicated mice, the last serving as model for MB induction. Hepatocyte cytokeratins become hyperphosphorylated at multiple sites in AH and in DDC-intoxicated mice. Hyperphosphorylation of CK8/18 occurred rapidly, after 1 day of DDC intoxication and preceded architectural changes of the cytoskeleton, In long-term DDC-intoxicated mice as well as in human AH, MBs preferentially contain hyperphosphorylated CK8/18 as compared with the cytoplasmic cytokeratin intermediate filament network suggesting that CK8/18 hyperphosphorylation may play a contributing role in MB pathogenesis. Furthermore, the site-specific phosphorylation of cytokeratin in different stages of MB induction provides indirect evidence for the involvement of a variety of protein kinases known to be activated in stress responses,mitosis, and apoptosis.

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Documento generato il 29/09/20 alle ore 20:22:35