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Isatin (indole-2,3-dione) is an endogenous regulator exhibiting various effects mediated by numerous isatin-binding proteins localized in different compartments of cells of the brain and peripheral tissues. It attenuates manifestations of experimental parkinsonism induced by administration of the MPTP neurotoxin and reduces the movement disorders characteristic of this disease. The molecular mechanisms of the neuroprotective action of isatin include its direct interaction with proteasomes, intracellular supramolecular complexes responsible for the targeted elimination of proteins. Incubation of fractions of 26S and 20S rabbit brain proteasomes, containing the whole spectrum of proteasomal subunits, as well as a number of proteasome-associated proteins, with isatin (100 μM) had a significant impact on the profile of released proteins. In the case of 26S proteasomes containing, in addition to the core part (20S proteasome), 19S regulatory subparticles, incubation with isatin resulted in a more than threefold increase in the number of dissociated proteins. In the case of 20S proteasomes (containing only the 20S core particle), incubation with isatin resulted in a significant decrease in the number of dissociated proteins compared to the control. Our results indicate an important role of the regulatory 19S subunit components in the formation of the proteasome subproteome and the sensitivity of these supramolecular complexes to isatin.Izatin (indol-2,3-dion) — éndogennyĭ reguliator, okazyvaiushchiĭ raznoobraznye éffekty, kotorye oposreduiutsia mnogochislennymi izatinsviazyvaiushchimi belkami, lokalizovannymi v razlichnykh kompartmentakh kletok mozga i perifericheskikh tkaneĭ. On proiavliaet svoĭstva neĭroprotektora, kotoryĭ v modeli éksperimental'nogo parkinsonizma, indutsirovannogo vedeniem neĭrotoksina MFTP, snizhaet dvigatel'nye narusheniia, svoĭstvennye étomu zabolevaniiu. Molekuliarnye mekhanizmy neĭroprotektornogo deĭstviia izatina vkliuchaiut ego priamoe vzaimodeĭstvie s proteasomami — vnutrikletochnymi nadmolekuliarnymi kompleksami, otvetstvennymi za targetnuiu éliminatsiiu belkov. Pri inkubatsii s izatinom (100 mkM) fraktsiĭ 26S i 20S proteasom mozga krolika, soderzhashchikh ves' spektr sobstvenno proteasomnykh sub"edinits, a takzhe riad assotsiirovannykh s proteasomami belkov, obnaruzheny sushchestvennye razlichiia v kolichestve i sostave vysvobodivshikhsia belkov. V sluchae 26S proteasom, soderzhashchikh, pomimo korovoĭ chasti (20S proteasoma), 19S reguliatornye subchastitsy, inkubatsiia s izatinom privodila k bolee chem trekhkratnomu uvelicheniiu chisla dissotsiirovavshikh belkov. V sluchae 20S proteasom (soderzhashchikh tol'ko korovuiu chast') inkubatsiia s izatinom privodila k sushchestvennomu snizheniiu chisla dissotsiirovavshikh belkov po sravneniiu s kontrolem. Poluchennye rezul'taty svidetel'stvuiut o vazhnoĭ roli komponentov reguliatornoĭ 19S subchastitsy v formirovanii subproteoma proteasom i chuvstvitel'nosti étikh nadmolekuliarnykh kompleksov k izatinu. |
