Gastroprotection by vitamin C--a heme oxygenase-1-dependent mechanism?
Free oxygen radicals contribute to gastric mucosal damage induced by acetylic-salicylic acid (ASA). Vitamin C has been shown to reduce gastric toxicity of ASA in humans. We intended to assess the role of heme oxygenase-1 (HO-1) in this process by application of these substances to AGS and KATO III cells. HO-1 expression was monitored by real-time RT-PCR, Western blot, and HO activity measurement. HO-1 mRNA was significantly elevated by either ASA or vitamin C in gastric epithelial cells, combination of both substances further increased expression. HO-1 protein and enzyme activity rose in cells exposed to vitamin C alone or combined with ASA, but not after stimulation with ASA alone. In contrast to endothelia, in which ASA simultaneously induces HO-1 mRNA and protein expression, gastric epithelial cells require vitamin C to translate HO-1 mRNA into active protein, which then may exert gastroprotection by its antioxidant and vasodilative properties.
Becker
Jan C
JC
Department of Medicine B, University of Münster, Münster, Germany.
Grosser
Nina
N
Boknik
Peter
P
Schröder
Henning
H
Domschke
Wolfram
W
Pohle
Thorsten
T
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology; D001205:Ascorbic Acid / Q000494:pharmacology*; D001241:Aspirin / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006801:Humans; D008565:Membrane Proteins; D013274:Stomach Neoplasms / Q000378:metabolism*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D008565:Membrane Proteins; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; D001205:Ascorbic Acid; D001241:Aspirin