title: Prevention of Barrier Disruption by Heme Oxygenase-1 in Intestinal Bleeding Model.
abstract: In this study we investigated the effect of free heme, the local level of which was increased by bleeding, on the intestinal barrier function, using human epithelial colorectal adenocarcinoma cells (Caco-2). Our results show that the addition of hemin to the culture medium markedly disrupted the barrier function, which was significantly improved by glutamine supplementation. Although hemin treatment caused the increased expression of heme oxygenase (HO)-1, the inhibition of HO activity resulted in the aggravation of hemin-induced barrier dysfunction. Up-regulation of HO-1 by pretreatment with a low concentration of hemin almost completely prevented hemin-induced barrier dysfunction. Taken together, these observations indicate that an abnormally high level of intracellular free heme causes barrier dysfunction, probably through the modulation of proteins forming tight junctions.
authors.affiliation: Department of Pharmacy, Faculty of Pharmacy, Yasuda Women's University.
authors.forename: Reiko
authors.initials: R
authors.lastname: Akagi
authors.forename: Masaaki
authors.initials: M
authors.lastname: Akagi
authors.forename: Yuta
authors.initials: Y
authors.lastname: Hatori
authors.forename: Sachiye
authors.initials: S
authors.lastname: Inouye
mesh_terms: D001205:Ascorbic Acid / Q000494:pharmacology; D018938:Caco-2 Cells; D006471:Gastrointestinal Hemorrhage / Q000378:metabolism*; D005973:Glutamine / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008315:Malondialdehyde / Q000378:metabolism; D008665:Metalloporphyrins / Q000494:pharmacology
chemical_list: D008665:Metalloporphyrins; C055421:tin mesoporphyrin; D005973:Glutamine; D008315:Malondialdehyde; D006427:Hemin; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D001205:Ascorbic Acid