Citations

ABSTRACTModifications of mucosal phospholipids have been detected in samples from patients withHelicobacter pylori-positive gastritis. These alterations appear secondary to increased phospholipase A2activity (PLA2). The cytosolic form of this enzyme (cPLA2), normally involved in cellular signaling and growth, has been implicated in cancer pathogenesis. The aim of this study was to investigate cPLA2expression and PLA2activity in the gastric mucosae of patients with and withoutH. pyloriinfection. In gastric biopsies from 10H. pylori-positive patients, cPLA2levels, levels of mRNA as determined by reverse transcriptase PCR, levels of protein as determined by immunohistochemistry, and total PLA2activity were higher than in 10H. pylori-negative gastritis patients. To clarify whetherH. pylorihad a direct effect on the cellular expression of cPLA2, we studied cPLA2expression in vitro with different human epithelial cell lines, one from a patient with larynx carcinoma (i.e., HEp-2 cells) and two from patients with gastric adenocarcinoma (i.e., AGS and MKN 28 cells), incubated with differentH. pyloristrains. The levels of cPLA2, mRNA, and protein expression were unchanged in Hep-2 cells independently of cellular adhesion or invasion of the bacteria. Moreover, no change in cPLA2protein expression was observed in AGS or MKN 28 cells treated with wild-typeH. pylori. In conclusion, our study shows increased cPLA2expression and PLA2activity in the gastric mucosae of patients withH. pyloriinfection and no change in epithelial cell lines exposed toH. pylori.

Nitric oxide (NO) and carbon monoxide (CO) seem to be neurotransmitters in the brain. The colocalization of their respective biosynthetic enzymes, neuronal NO synthase (nNOS) and heme oxygenase-2 (HO2), in enteric neurons and altered intestinal function in mice with genomic deletion of the enzymes ( nNOS Δ/Δ and HO2 Δ/Δ ) suggest neurotransmitter roles for NO and CO in the enteric nervous system. We now establish that NO and CO are both neurotransmitters that interact as cotransmitters. Small intestinal smooth muscle cells from nNOS Δ/Δ and HO2 Δ/Δ mice are depolarized, with apparent additive effects in the double knockouts ( HO2 Δ/Δ / nNOS Δ/Δ ). Muscle relaxation and inhibitory neurotransmission are reduced in the mutant mice. In HO2 Δ/Δ preparations, responses to electrical field stimulation are nearly abolished despite persistent nNOS expression, whereas exogenous CO restores normal responses, indicating that the NO system does not function in the absence of CO generation.