The Helicobacter pylori fatty acid cis-9,10-methyleneoctadecanoic acid stimulates protein kinase C and increases DNA synthesis of gastric HM02 cells.
Protein kinase C (PKC) has been implicated in the control of epithelial proliferative activity and in the process of malignant transformation. Helicobacter pylori (H.p.) infection is associated with increased gastric epithelial cell proliferation and has been linked with gastric carcinoma. In the present study, we report that the H.p. fatty acid cis-9,10-methyleneoctadecanoic acid (MOA) directly activates PKC (Ka 3.3 microM). The effect of MOA upon PKC activation was Ca2+ dependent but did not require phosphatidylserine as phospholipid cofactor. MOA increased the stimulatory effect of phosphatidylserine at low Ca2+ (1 microM) concentrations. These findings indicate that MOA interacts at the phospholipid- and the diacylglycerol-binding domain to elicit PKC activation. Treatment of gastric mucous cells HM02 caused translocation of PKC from the cytosol to the nuclear, mitochondrial and membrane fraction. Furthermore, MOA stimulated [3H]thymidine incorporation into the DNA of HM02 cells. Our results show that the H.p. fatty acid MOA activates PKC and increases DNA synthesis in gastric epithelial cells.
Department of General Pharmacology, Hannover Medical School, Germany.
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D000818:Animals; D004247:DNA / Q000096:biosynthesis*; D004789:Enzyme Activation / Q000187:drug effects; D005227:Fatty Acids / Q000494:pharmacology*; D016480:Helicobacter pylori / Q000737:chemistry / Q000502:physiology*; D006801:Humans; D011493:Protein Kinase C / Q000032:analysis / Q000187:drug effects*; D051381:Rats; D013274:Stomach Neoplasms / Q000201:enzymology / Q000209:etiology* / Q000473:pathology
D005227:Fatty Acids; C029355:dihydrosterculic acid; D004247:DNA; D011493:Protein Kinase C