A protective role of hydrogen sulfide against oxidative stress in rat gastric mucosal epithelium.
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.
Yonezawa
Daiki
D
Division of Pharmacology and Pathophysiology, Kinki University School of Pharmacy, 3-4-1 Kowakae, Higashi-osaka 577-8502, Japan.
Sekiguchi
Fumiko
F
Miyamoto
Misato
M
Taniguchi
Eiichi
E
Honjo
Masami
M
Masuko
Takashi
T
Nishikawa
Hiroyuki
H
Kawabata
Atsufumi
A
D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D006690:Bisbenzimidazole; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004847:Epithelial Cells / Q000187:drug effects*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000473:pathology*; D005905:Glyburide / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000633:toxicity; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D007004:Hypoglycemic Agents / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D054086:KATP Channels / Q000378:metabolism; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity; D018384:Oxidative Stress / Q000187:drug effects*; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D011955:Receptors, Drug; D015427:Reperfusion Injury / Q000473:pathology / Q000517:prevention & control; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D064233:Sulfonylurea Receptors