title: A pore-forming toxin produced by Aeromonas sobria activates Ca2+ dependent Cl- secretion.
abstract: Bacteria produce many types of hemolysin that induce diarrhea by mechanisms that are not completely understood. Aeromonas sobria hemolysin (ASH) is a major virulence factor produced by A. sobria, a human pathogen that causes diarrhea. Since epithelial cells in the intestine are the primary targets of hemolysin, we investigated the effects of ASH on ion transport in human colonic epithelial (Caco-2) cells. ASH increased short-circuit currents (Isc) in a dose-dependent manner, and it also activated a 125I efflux from Caco-2 cells. ASH-induced Isc increases and 125I efflux activations were both suppressed by low Ca2+ levels in the extracellular solution or by pretreatment with the Ca2+ chlelator BAPTA-AM. Intracellular Ca2+ levels were increased by ASH in a biphasic fashion characterized by a rapid sharp increase (peak 1) followed by a sustained low plateau (peak 2). ASH-induced peak 1 was inhibited by pretreatment with pertussis toxin, indicating that Ca2+ was mobilized from intracellular stores, and peak 2 was induced by an influx of extracellular Ca2+. Peak 2 but not peak 1 was related to Cl- secretion. These results indicate that ASH activates Ca2+-dependent Cl- secretion.
authors.affiliation: Department of Nutrition and Metabolism, Institute of Health Biosciences, The University of Tokushima Graduate School, 3-18-5 Kuramoto-cho, Tokushima City, Tokushima 770-8503, Japan. akiratak@nutr.med.tokushima-u.ac.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Takahashi
authors.forename: Naomi
authors.initials: N
authors.lastname: Tanoue
authors.forename: Masayuki
authors.initials: M
authors.lastname: Nakano
authors.forename: Akiko
authors.initials: A
authors.lastname: Hamamoto
authors.forename: Keinosuke
authors.initials: K
authors.lastname: Okamoto
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Fujii
authors.forename: Nagakatsu
authors.initials: N
authors.lastname: Harada
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakaya
mesh_terms: D000333:Aeromonas / Q000502:physiology*; D018938:Caco-2 Cells; D002118:Calcium / Q000502:physiology*; D002614:Chelating Agents / Q000494:pharmacology; D002712:Chlorides / Q000502:physiology*; D003967:Diarrhea / Q000382:microbiology; D004533:Egtazic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006460:Hemolysin Proteins / Q000502:physiology*; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D008564:Membrane Potentials / Q000502:physiology; D037342:Pertussis Toxin / Q000494:pharmacology
chemical_list: D002614:Chelating Agents; D002712:Chlorides; D006460:Hemolysin Proteins; C070379:1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester; D004533:Egtazic Acid; D037342:Pertussis Toxin; D002118:Calcium