Tin protoporphyrin induces intestinal chloride secretion by inducing light oxidation processes

Aliye Uc; Krzysztof J Reszka; Garry R Buettner; John B Stokes

doi:10.1152/ajpcell.00550.2006

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Tin protoporphyrin induces intestinal chloride secretion by inducing light oxidation processes

Journal article

Peer reviewed

Tin protoporphyrin induces intestinal chloride secretion by inducing light oxidation processes

Aliye Uc, Krzysztof J Reszka, Garry R Buettner and John B Stokes

American Journal of Physiology: Cell Physiology, Vol.292(5), pp.C1906-1914

05/2007

DOI: 10.1152/ajpcell.00550.2006

PMID: 17215323

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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.

Intestinal Mucosa - radiation effects

Intestinal Mucosa - metabolism

Epithelial Cells - metabolism

Reactive Oxygen Species - metabolism

Chloride Channels - drug effects

Epithelial Cells - drug effects

Humans

Nitrobenzoates - pharmacology

Protoporphyrins - pharmacology

Carbon Monoxide - metabolism

Metalloporphyrins - pharmacology

Intestinal Mucosa - drug effects

Dose-Response Relationship, Drug

Hemin - metabolism

Time Factors

Chlorides - metabolism

Light

Oxidative Stress - radiation effects

Heme Oxygenase (Decyclizing) - antagonists & inhibitors

Heme Oxygenase (Decyclizing) - metabolism

alpha-Tocopherol - pharmacology

Ouabain - pharmacology

Caco-2 Cells

Membrane Potentials - drug effects

Epithelial Cells - radiation effects

Oxidation-Reduction

Enzyme Inhibitors - pharmacology

Antioxidants - pharmacology

Chloride Channels - metabolism

Intestinal Secretions - drug effects

Ascorbic Acid - pharmacology

Oxidative Stress - drug effects

Details

Title: Subtitle: Tin protoporphyrin induces intestinal chloride secretion by inducing light oxidation processes
Creators: Aliye Uc - The University of Iowa, Carver College of Medicine, Iowa City, IA 52242, USA. aliye-uc@uiowa.edu
Krzysztof J Reszka
Garry R Buettner
John B Stokes
Resource Type: Journal article
Publication Details: American Journal of Physiology: Cell Physiology, Vol.292(5), pp.C1906-1914
Publisher: United States
DOI: 10.1152/ajpcell.00550.2006
PMID: 17215323
ISSN: 0363-6143
eISSN: 1522-1563
Grant note: DK-63135 / NIDDK NIH HHS DK-52617 / NIDDK NIH HHS
Language: English
Date published: 05/2007
Academic Unit: Stead Family Department of Pediatrics; Radiation Oncology; Gastroenterology, Hepatology, Pancreatology, and Nutrition
Record Identifier: 9984046802402771

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