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Tissue-nonspecific alkaline phosphatase is activated in enterocytes by oxidative stress via changes in glycosylation.
MedLine Citation:
PMID:  20645320     Owner:  NLM     Status:  In-Process    
BACKGROUND: Intestinal inflammation produces an induction of alkaline phosphatase (AP) activity that is attributable in part to augmented expression, accompanied by a change in isoform, in epithelial cells.
METHODS: This study focuses on induction of AP in intestinal epithelial cells in vitro.
RESULTS: Treatment with the oxidants H2O2, monochloramine, or tButOOH increases AP activity in vitro in Caco-2, HT29, and IEC18 cells. We selected IEC18 cells for further testing. Basal AP activity in IEC18 cells is of the tissue-nonspecific (bone-liver-kidney) type, as indicated by Northern and Western blot analysis. Oxidative stress augments AP activity and the sensitivity of the enzyme to levamisole, homoarginine, and heat in IEC18 cells. Increased immunoreactivity to tissue-nonspecific AP antibodies suggests an isoform shift from liver to either kidney or bone type. This effect occurs without changes at the mRNA level and is sensitive to tunicamycin, an inhibitor of N-glycosylation, and neuraminidase digestion. Saponin and deoxycholate produce similar effects to oxidants. Butyrate but not proinflammatory cytokines or LPS can induce a similar effect but without toxicity. The AP increase is not prevented by modulators of the MAPK, NF-κB, calcium, and cyclic adenosine monophosphate (cAMP) pathways, and is actually enhanced by actinomycin D via higher cell stress.
CONCLUSIONS: Oxidative stress causes a distinct increase in enterocyte AP activity together with cell toxicity via changes in the glycosylation of the enzyme that correspond to a shift in isotype within the tissue-nonspecific paradigm. We speculate that this may have physiological implication for gut defense.
Rocío López-Posadas; Raquel González; Isabel Ballester; Patricia Martínez-Moya; Isabel Romero-Calvo; María Dolores Suárez; Antonio Zarzuelo; Olga Martínez-Augustin; Fermín Sánchez de Medina
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Inflammatory bowel diseases     Volume:  17     ISSN:  1536-4844     ISO Abbreviation:  Inflamm. Bowel Dis.     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-12     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9508162     Medline TA:  Inflamm Bowel Dis     Country:  United States    
Other Details:
Languages:  eng     Pagination:  543-56     Citation Subset:  IM    
Department of Pharmacology, School of Pharmacy, University of Granada, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Campus de Cartuja, Granada, Spain.
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