American Chemical Society, Journal of Proteome Research, 5(13), p. 2433-2444, 2014
DOI: 10.1021/pr500192g
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mTor plays a central role in controlling protein homeostasis and cell survival. Recently, we have demonstrated that perturbations of mTor signaling are implicated in Alzheimer's disease (AD), and that mTor complex 1 (mTorC1) is involved in the formation of toxic phospho-tau. Therefore, we employed mass spectrometry- based proteomics to identify specific protein expression changes in relation with cell survival in human neuroblastoma SH-SY5Y cells expressing genetically modified mTor. Cell death in SH-SY5Y cells was induced by moderate serum deprivation. Using flow cytometry we observed that up-regulated mTor complex 2 (mTorC2) increases the number of viable cells. By using a combination approach of proteomic and enrichment analysis we have identified several proteins (thioredoxin-dependent peroxide reductase, peroxiredoxin-5, cofilin 1 (non-muscle), Annexin A5, mortalin, and 14-3-3 protein zeta/delta) involved in mitochondrial integrity, apoptotic and pro-survival functions (caspase inhibitor activity and anti-apoptosis), and they were significantly altered by mTor activity modulation. The major findings of this study are the implication of mTorC2 but not mTorC1 in cell viability modulation by activating the pro-survival machinery. Taken together, these results suggest that up-regulated mTorC2 might be playing important role in promoting cell survival by suppressing mitochondria-caspase-apoptotic pathway in vitro.