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

Bull Exp Biol Med. 2021 Dec;172(2):270-275. doi: 10.1007/s10517-021-05374-2. Epub 2021 Dec 2.

Abstract

Incubation of primary culture of pulmonary fibroblasts with non-opiate analogue of leuenkephalin (NALE; Phe-D-Ala-Gly-Phe-Leu-Arg, 0.1 μM) 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 μM). 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 μM) 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.

Keywords: cytoprotective effect; oxidative stress; peptide analogue of leu-enkephalin.

MeSH terms

  • Animals
  • Arginine / pharmacology
  • Arginine / physiology*
  • Cells, Cultured
  • Cytoprotection / drug effects
  • Enkephalin, Leucine / analogs & derivatives
  • Enkephalin, Leucine / pharmacology*
  • Fibroblasts / drug effects
  • Fibroblasts / physiology
  • Hydrogen Peroxide / pharmacology
  • Lung / cytology
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Nitric Oxide / pharmacology
  • Nitric Oxide / physiology*
  • Oxidative Stress / drug effects
  • Protective Agents / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • Protective Agents
  • Nitric Oxide
  • Enkephalin, Leucine
  • Arginine
  • Hydrogen Peroxide
  • NG-Nitroarginine Methyl Ester