The key role of the regulatory 19S subunit in changes in the brain proteasome subproteome induced by the neuroprotector isatin

   
Buneeva O.A.1 , Kopylov A.T.1, Medvedev A.E.1

1. Institute of Biomedical Chemistry, Moscow, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20226804250      PubMed Id: 36005843
Year: 2022  Volume: 68  Issue: 4  Pages: 250-262
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.
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Keywords: 26S and 20S proteasomes, subproteome, interactome, isatin, neuroprotector, proteasome core, regulatory subunit
Citation:

Buneeva, O. A., Kopylov, A. T., Medvedev, A. E. (2022). The key role of the regulatory 19S subunit in changes in the brain proteasome subproteome induced by the neuroprotector isatin. Biomeditsinskaya Khimiya, 68(4), 250-262.
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