Role of Amino Acid Arginine and Nitric Oxide in Mechanisms of Cytoprotective Effect of Non-Opiate Leu-Enkephalin Analogue In Vitro

摘要

Incubation of primary culture of pulmonary fibroblasts with non-opiate analogue of leuenkephalin (NALE; Phe-D-Ala-Gly-Phe-Leu-Arg, 0.1 mu M) reduced generation of superoxide anion-radical (by 20.7) and decreased the number of p53(+) cells (by 40.2) induced by exposure to H2O2 (60 mu M). The cytoprotective effect of NALE was potentiated by NO synthase inhibitor L-NAME (1 mM): the number of p53(+) cells decreased by 65.3 and morphometric parameters of the cell nuclei and nucleoli were improved. Incubation of pulmonary fibroblasts culture with peptide G (Phe-D-Ala-Gly-Phe-Leu-Gly, 0.1 mu M) also significantly reduced the damaging effect of H2O2: the number of p53(+) cells decreased by 73.5, the area of cell nuclei returned to normal, and generation of superoxide anion-radical decreased by 18.4. These results indicate that C-terminal amino acid Arg and activation of NO synthase are not involved in the direct cytoprotective effect of NALE.