Effects of proteasome inhibitor, MG132, on proteasome activity and oxidative status of rat liver.
In vivo effects of N-benzyloxycarbonyl (Cbz)-Leu-Leu-leucinal (MG132) on chymotryptic-like (ChT-L), tryptic-like, and post-glutamyl peptide hydrolytic-like proteasome activities, protein oxidation, lipid peroxidation (LP), glutathione (GSH) level, as well as on the activity of antioxidant enzymes (superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), and glutathione-reductase) in the rat liver were studied. The possibility of MG132 provoking the formation of free oxygen radicals was also assayed in primary hepatocytes. The following results were obtained: (1) In vivo, MG132 did not change the spontaneous LP, but increased Fe-induced LP and the amount of oxidized proteins; it decreased the GSH level in liver. From the proteasome activities studied in liver cytosol only ChT-L activity was significantly decreased after MG132 administration. Furthermore, MG132 increased antioxidant enzyme activities of SOD, CAT, and GSH-Px. (2) In vitro, MG132 increased free radical oxygen species in hepatocytes; this effect disappeared in the presence of CAT or mannitol. In conclusion, since nowadays proteasome inhibitors are entering into the swing of laboratory and clinical practice, the present data could provide useful information for MG132 action. Consequently, future in vivo experiments with MG132 could highlight the possibility of its use at different pathological conditions.
Alexandrova
Albena
A
Institute of Neurobiology, Bulgarian Academy of Sciences, Sofia, Bulgaria. a_alexandrova_bas@yahoo.com
Petrov
Lubomir
L
Georgieva
Almira
A
Kirkova
Margarita
M
Kukan
Marian
M
D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007274:Injections, Intraperitoneal; D007976:Leupeptins / Q000008:administration & dosage / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D018384:Oxidative Stress / Q000187:drug effects*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D061988:Proteasome Inhibitors; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D007976:Leupeptins; D061988:Proteasome Inhibitors; D017382:Reactive Oxygen Species; D046988:Proteasome Endopeptidase Complex; D005978:Glutathione; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde