title: Regulation of prolyl endopeptidase activity by the intracellular redox state.
abstract: The activity of prolyl endopeptidase was markedly decreased during incubation of intact murine erythroleukemia cells at 45 degrees C, but not during incubation of sonicated cells or during incubation at 42 degrees C. The thermal inactivation of prolyl endopeptidase in situ required neither the synthesis of proteins and polynucleotides nor the synergistic activation of inhibitors. Moreover, inhibition of lysosomal proteinases and calpains or depletion of ATP did not affect the thermal inactivation of prolyl endopeptidase. This specific inactivation of prolyl endopeptidase was also observed following the addition to the culture medium of menadione or diamide, compounds known to increase intracellular oxidized glutathione levels. The activity of prolyl endopeptidase in the cell lysate was also dose-dependently decreased by the addition of glutathione disulfide and the decrease of the activity was prevented by coexistence of reduced glutathione. Furthermore, the level of intracellular oxidized glutathione was increased during incubation at 45 degrees C for 15 min, but not at 42 degrees C for 30 min. These results strongly suggest that the activity of prolyl endopeptidase is regulated by changes in the intracellular redox potential.
authors: National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo, Japan.
authors: T
authors: T
authors: Tsukahara
authors: S
authors: S
authors: Ishiura
authors: H
authors: H
authors: Sugita
mesh_terms: D000818:Animals; D004220:Disulfides; D010450:Endopeptidases / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism*; D006358:Hot Temperature; D004915:Leukemia, Erythroblastic, Acute; D051379:Mice; D010084:Oxidation-Reduction; D011392:Proline; D000085822:Prolyl Oligopeptidases; D012697:Serine Endopeptidases; D013312:Stress, Physiological / Q000201:enzymology; D014407:Tumor Cells, Cultured
chemical_list: D004220:Disulfides; D011392:Proline; D010450:Endopeptidases; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases; D005978:Glutathione