Abstract
We investigated effect of hydrogen sulfide (H(2)S) on oxidative stress-caused cell death in gastric mucosal epithelial cells. In rat normal gastric epithelial RGM1 cells, NaHS, a H(2)S donor, at 1.5mM strongly suppressed hydrogen peroxide (H(2)O(2))-caused cell death, while it slightly augmented the H(2)O(2) toxicity at 0.5-1mM. The protective effect of NaHS was abolished by inhibitors of MEK or JNK, but not of p38 MAP kinase. NaHS at 1.5mM actually phosphorylated ERK and JNK in RGM1 cells. Glibenclamide, an ATP-sensitive K(+) (K(ATP)(+)) channel inhibitor, did not affect the protective effect of NaHS, although mRNAs for K(ATP)(+) channel subunits, Kir6.1 and SUR1, were detected in RGM1 cells. In anesthetized rats, oral administration of NaHS protected against gastric mucosal lesion caused by ischemia-reperfusion. These results suggest that NaHS/H(2)S may protect gastric mucosal epithelial cells against oxidative stress through stimulation of MAP kinase pathways, a therapeutic dose range being very narrow.
MeSH terms
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ATP-Binding Cassette Transporters / metabolism
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Air Pollutants / pharmacology*
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Animals
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Apoptosis / drug effects
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Bisbenzimidazole
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Cell Death / drug effects
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Cell Line
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Epithelial Cells / drug effects*
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Extracellular Signal-Regulated MAP Kinases / metabolism
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Gastric Mucosa / drug effects
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Gastric Mucosa / pathology*
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Glyburide / pharmacology
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Hydrogen Peroxide / toxicity
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Hydrogen Sulfide / pharmacology*
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Hypoglycemic Agents / pharmacology
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JNK Mitogen-Activated Protein Kinases / metabolism
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KATP Channels / metabolism
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Multidrug Resistance-Associated Proteins / metabolism
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Oxidants / toxicity
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Oxidative Stress / drug effects*
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Potassium Channels, Inwardly Rectifying / metabolism
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RNA, Messenger / biosynthesis
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RNA, Messenger / genetics
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Rats
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Receptors, Drug
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Reperfusion Injury / pathology
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Reperfusion Injury / prevention & control
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Reverse Transcriptase Polymerase Chain Reaction
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Sulfonylurea Receptors
Substances
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ATP-Binding Cassette Transporters
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Abcc8 protein, rat
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Air Pollutants
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Hypoglycemic Agents
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KATP Channels
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Multidrug Resistance-Associated Proteins
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Oxidants
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Potassium Channels, Inwardly Rectifying
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RNA, Messenger
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Receptors, Drug
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Sulfonylurea Receptors
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uK-ATP-1 potassium channel
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Hydrogen Peroxide
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Extracellular Signal-Regulated MAP Kinases
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JNK Mitogen-Activated Protein Kinases
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Bisbenzimidazole
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Glyburide
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Hydrogen Sulfide