Tags

Type your tag names separated by a space and hit enter

Roles of ZO-1, occludin, and actin in oxidant-induced barrier disruption.
Am J Physiol Gastrointest Liver Physiol. 2006 Feb; 290(2):G222-31.AJ

Abstract

Oxidants such as monochloramine (NH(2)Cl) decrease epithelial barrier function by disrupting perijunctional actin and possibly affecting the distribution of tight junctional proteins. These effects can, in theory, disturb cell polarization and affect critical membrane proteins by compromising molecular fence function of the tight junctions. To examine these possibilities, we investigated the actions of NH(2)Cl on the distribution, function, and integrity of barrier-associated membrane, cytoskeletal, and adaptor proteins in human colonic Caco-2 epithelial monolayers. NH(2)Cl causes a time-dependent decrease in both detergent-insoluble and -soluble zonula occludens (ZO)-1 abundance, more rapidly in the former. Decreases in occludin levels in the detergent-insoluble fraction were observed soon after the fall of ZO-1 levels. The actin depolymerizer cytochalasin D resulted in a decreased transepithelial resistance (TER) more quickly than NH(2)Cl but caused a more modest and slower reduction in ZO-1 levels and in occludin redistribution. No changes in the cellular distribution of claudin-1, claudin-5, or ZO-2 were observed after NH(2)Cl. However, in subsequent studies, the immunofluorescent cellular staining pattern of all these proteins was altered by NH(2)Cl. The actin-stabilizing agent phalloidin did not prevent NH(2)Cl-induced decreases in TER or increases of apical to basolateral flux of the paracellular permeability marker mannitol. However, it partially blocked changes in ZO-1 and occludin distribution. Tight junctional fence function was also compromised by NH(2)Cl, observed as a redistribution of the alpha-subunit of basolateral Na(+)-K(+)-ATPase to the apical membrane, an effect not found with the apical membrane protein Na(+)/H(+) exchanger isoform 3. In conclusion, oxidants not only disrupt perijunctional actin but also cause redistribution of tight junctional proteins, resulting in compromised intestinal epithelial barrier and fence function. These effects are likely to contribute to the development of malabsorption and dysfunction associated with mucosal inflammation of the digestive tract.

Authors+Show Affiliations

The University of Chicago Hospitals, 5841 S. Maryland Ave., MC 6084, Chicago, IL 60637, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16239402

Citation

Musch, Mark W., et al. "Roles of ZO-1, Occludin, and Actin in Oxidant-induced Barrier Disruption." American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 290, no. 2, 2006, pp. G222-31.
Musch MW, Walsh-Reitz MM, Chang EB. Roles of ZO-1, occludin, and actin in oxidant-induced barrier disruption. Am J Physiol Gastrointest Liver Physiol. 2006;290(2):G222-31.
Musch, M. W., Walsh-Reitz, M. M., & Chang, E. B. (2006). Roles of ZO-1, occludin, and actin in oxidant-induced barrier disruption. American Journal of Physiology. Gastrointestinal and Liver Physiology, 290(2), G222-31.
Musch MW, Walsh-Reitz MM, Chang EB. Roles of ZO-1, Occludin, and Actin in Oxidant-induced Barrier Disruption. Am J Physiol Gastrointest Liver Physiol. 2006;290(2):G222-31. PubMed PMID: 16239402.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Roles of ZO-1, occludin, and actin in oxidant-induced barrier disruption. AU - Musch,Mark W, AU - Walsh-Reitz,Margaret Mary, AU - Chang,Eugene B, Y1 - 2005/10/20/ PY - 2005/10/22/pubmed PY - 2006/3/3/medline PY - 2005/10/22/entrez SP - G222 EP - 31 JF - American journal of physiology. Gastrointestinal and liver physiology JO - Am J Physiol Gastrointest Liver Physiol VL - 290 IS - 2 N2 - Oxidants such as monochloramine (NH(2)Cl) decrease epithelial barrier function by disrupting perijunctional actin and possibly affecting the distribution of tight junctional proteins. These effects can, in theory, disturb cell polarization and affect critical membrane proteins by compromising molecular fence function of the tight junctions. To examine these possibilities, we investigated the actions of NH(2)Cl on the distribution, function, and integrity of barrier-associated membrane, cytoskeletal, and adaptor proteins in human colonic Caco-2 epithelial monolayers. NH(2)Cl causes a time-dependent decrease in both detergent-insoluble and -soluble zonula occludens (ZO)-1 abundance, more rapidly in the former. Decreases in occludin levels in the detergent-insoluble fraction were observed soon after the fall of ZO-1 levels. The actin depolymerizer cytochalasin D resulted in a decreased transepithelial resistance (TER) more quickly than NH(2)Cl but caused a more modest and slower reduction in ZO-1 levels and in occludin redistribution. No changes in the cellular distribution of claudin-1, claudin-5, or ZO-2 were observed after NH(2)Cl. However, in subsequent studies, the immunofluorescent cellular staining pattern of all these proteins was altered by NH(2)Cl. The actin-stabilizing agent phalloidin did not prevent NH(2)Cl-induced decreases in TER or increases of apical to basolateral flux of the paracellular permeability marker mannitol. However, it partially blocked changes in ZO-1 and occludin distribution. Tight junctional fence function was also compromised by NH(2)Cl, observed as a redistribution of the alpha-subunit of basolateral Na(+)-K(+)-ATPase to the apical membrane, an effect not found with the apical membrane protein Na(+)/H(+) exchanger isoform 3. In conclusion, oxidants not only disrupt perijunctional actin but also cause redistribution of tight junctional proteins, resulting in compromised intestinal epithelial barrier and fence function. These effects are likely to contribute to the development of malabsorption and dysfunction associated with mucosal inflammation of the digestive tract. SN - 0193-1857 UR - https://www.unboundmedicine.com/medline/citation/16239402/Roles_of_ZO_1_occludin_and_actin_in_oxidant_induced_barrier_disruption_ L2 - https://journals.physiology.org/doi/10.1152/ajpgi.00301.2005?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -