Proteome analysis of PC12 cells reveals alterations in translation regulation and actin signalling induced by clozapine

ABSTRACT: Although antipsychotics are routinely used in the treatment of schizophrenia for last decades, their precise mechanism of action is still unclear. In this study we investigated changes in PC12 cells’ proteome under the influence of clozapine, risperidone and haloperidol to identify protein pathways regulated by the antipsychotics. Analysis of the protein profiles in two time points: after 12 and 24 h of incubation with drugs revealed significant alterations in 510 proteins. Further canonical pathway analysis determined signal transduction pathways and biological processes regulatednby drug treatment. Interestingly, all tested drugs have caused changes in PC12 proteome which correspond to inhibition of cytokines: tumor necrosis factor (TNF) and transforming growth factor beta 1 (TGF-β1), what can be linked to the immunological and viral hypothesis of schizophrenia. We found, that the 12-hour incubation with clozapine caused up-regulation of protein kinase A signalling and translation machinery. After 24 h of treatment with clozapine, the inhibition of the actin cytoskeleton signalling and Rho proteins signalling was revealed. Obtained results suggests that mammalian target of rapamycin complex 1 (mTORC1) and 2 (mTORC2) play a central role in the signal transduction of clozapine.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Rattus Norvegicus (rat)

TISSUE(S): Cell Culture

SUBMITTER: Urszula Jankowska  

LAB HEAD: Sylwia Kędracka-Krok

PROVIDER: PXD014422 | Pride | 2021-09-08

REPOSITORIES: Pride