Stimulation of intralysosomal proteolysis by cysteinyl-glycine, a product of the action of gamma-glutamyl transpeptidase on glutathione.
The mechanism of the stimulatory effect of glutathione on proteolysis in mouse kidney lysosomes and a lack of an effect in lysosomes from the liver was investigated. The stimulation in kidney lysosomes was inhibited by serine plus borate, a reversibly inhibitor of gamma-glutamyl transpeptidase. Treatment of mouse kidney lysosome suspensions with L-(alpha S,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (acivicin), an irreversibly inhibitor of the transpeptidase, also inhibited the effect of glutathione, but this inhibition was completely relieved by washing and addition of freshly prepared kidney membranes or purified gamma-glutamyl transpeptidase to the incubation mixtures. Cysteinyl-glycine, a product of the action of gamma-glutamyl transpeptidase, stimulated proteolysis in acivicin-inhibited kidney lysosome preparations similarly to glutathione, and cysteine had no effect at equivalent concentrations. Glutathione also stimulated proteolysis in liver lysosomes in the presence of washed kidney membranes or gamma-glutamyl transpeptidase, but the effect was similar to that produced by equivalent concentrations of cysteine. These results suggest that the stimulatory effect of glutathione was mediated by the action of gamma-glutamyl transpeptidase present in contaminating cell membrane fragments in the lysosome preparations, and that glutathione does not take part in intralysosomal proteolysis. However, the possibility that cysteinyl-glycine is a physiological intralysosomal disulfide reductant in kidney lysosomes has not been excluded.
Mego
J L
JL
D000818:Animals; D001881:Borates / Q000494:pharmacology; D003545:Cysteine / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005978:Glutathione / Q000494:pharmacology*; D007555:Isoxazoles / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology; D008099:Liver / Q000201:enzymology; D008247:Lysosomes / Q000201:enzymology*; D051379:Mice; D010447:Peptide Hydrolases / Q000378:metabolism; D051381:Rats; D012694:Serine / Q000494:pharmacology; D005723:gamma-Glutamyltransferase / Q000378:metabolism*
D001881:Borates; D004151:Dipeptides; D007555:Isoxazoles; D012694:Serine; D005723:gamma-Glutamyltransferase; D010447:Peptide Hydrolases; D005978:Glutathione; D003545:Cysteine; C006303:acivicin