This study reports a relationship between Akt3 expression and tissue-specific regulation of the pI3K/Akt/mTOR signaling pathway by copaiba essential oil. Akt3, a protein kinase B isoform important for the regulation of neuronal development, exhibited differential expression levels in cells of various origins. In neuronal and microglial cells, where Akt3 is present, copaiba essential oil positively regulated the pI3K/Akt/mTOR signaling pathway. In contrast, in liver cells and T lymphocytes, where Akt3 is absent, copaiba essential oil negatively regulated the pI3K/Akt/mTOR signaling pathway. The expression of Akt3 via plasmid DNA in liver cells led to positive regulatory effects by copaiba essential oil on the pI3K/Akt/mTOR signaling pathway. In contrast, inhibition of Akt3 expression in neuronal cells via small interfering RNA molecules targeting Akt3 transcripts abrogated the regulatory effects of copaiba essential oil on the pI3K/Akt/mTOR signaling pathway. Interestingly, Akt3 expression did not impact the regulatory effects of copaiba essential oil on other signaling pathways. For example, copaiba essential oil consistently upregulated the MAPK and JAK/STAT signaling pathways in all evaluated cell types, independent of the Akt3 expression level. Collectively, the data indicated that Akt3 expression was required for the positive regulatory effects of copaiba essential oil, specifically on the pI3K/Akt/mTOR signaling pathway.
Keywords: JAK/STAT; MAPK; capillary isoelectric focusing; copaiba essential oil; inflammation; nanofluidic proteomics; neuronal signaling pathways; neuropathic pain; pI3K/Akt/mTOR; protein post-translational modification.