title: Tin protoporphyrin induces intestinal chloride secretion by inducing light oxidation processes.
abstract: Heme induces Cl(-) secretion in intestinal epithelial cells, most likely via carbon monoxide (CO) generation. The major source of endogenous CO comes from the degradation of heme via heme oxygenase (HO). We hypothesized that an inhibitor of HO activity, tin protoporphyrin (SnPP), may inhibit the stimulatory effect of heme on Cl(-) secretion. To test this hypothesis, we treated an intestinal epithelial cell line (Caco-2 cells) with SnPP. In contrast to our expectations, Caco-2 cells treated with SnPP had an increase in their short-circuit currents (I(sc)) in Ussing chambers. This effect was observed only when the system was exposed to ambient light. SnPP-induced I(sc) was caused by Cl(-) secretion because it was inhibited in Cl(-)-free medium, with ouabain or 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB). The Cl(-) secretion was not via activation of the CFTR, because a specific inhibitor had no effect. Likewise, inhibitors of adenylate cyclase and guanylate cyclase had no effect on the enhanced I(sc). SnPP-induced I(sc) was inhibited by the antioxidant vitamins, alpha-tocopherol and ascorbic acid. Electron paramagnetic resonance experiments confirmed that oxidative reactions were initiated with light in cells loaded with SnPP. These data suggest that SnPP-induced effects may not be entirely due to the inhibition of HO activity but rather to light-induced oxidative processes. These novel effects of SnPP-photosensitized oxidation may also lead to a new understanding of how intestinal Cl(-) secretion can be regulated by the redox environment of the cell.
authors.affiliation: The University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA. aliye-uc@uiowa.edu
authors.forename: Aliye
authors.initials: A
authors.lastname: Uc
authors.forename: Krzysztof J
authors.initials: KJ
authors.lastname: Reszka
authors.forename: Garry R
authors.initials: GR
authors.lastname: Buettner
authors.forename: John B
authors.initials: JB
authors.lastname: Stokes
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology; D018938:Caco-2 Cells; D002248:Carbon Monoxide / Q000378:metabolism; D018118:Chloride Channels / Q000187:drug effects / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006427:Hemin / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D007419:Intestinal Secretions / Q000187:drug effects; D008027:Light; D008564:Membrane Potentials / Q000187:drug effects; D008665:Metalloporphyrins / Q000494:pharmacology*; D009579:Nitrobenzoates / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects* / Q000528:radiation effects; D011524:Protoporphyrins / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors; D024502:alpha-Tocopherol / Q000494:pharmacology
chemical_list: D000975:Antioxidants; D018118:Chloride Channels; D002712:Chlorides; D004791:Enzyme Inhibitors; D008665:Metalloporphyrins; D009579:Nitrobenzoates; D011524:Protoporphyrins; D017382:Reactive Oxygen Species; C058176:5-nitro-2-(3-phenylpropylamino)benzoic acid; D010042:Ouabain; D006427:Hemin; D002248:Carbon Monoxide; C032628:tin protoporphyrin IX; D006419:Heme Oxygenase (Decyclizing); D024502:alpha-Tocopherol; D001205:Ascorbic Acid