Protective effects of PIK3CG knockdown against OGD/R-induced neuronal damage via inhibition of autophagy through the AMPK/mTOR pathway.

Abstract

Background: Ischemic stroke represents an urgent need for more efficacious therapies owing to modest effectiveness of current treatment.

Methods: Download data from stroke patients and collect blood samples from clinical patients to analyze phosphatidylinositol-3 kinase catalytic subunit γ (PIK3CG) expression. To establish a brain damage model, oxygen glucose deprivation/reperfusion (OGD/R) was applied to SH-SY5Y cells. Impact of PIK3CG on AMPK/mTOR autophagy pathway was verified treating cells with AMPK activator metformin. Proliferation and apoptosis were identified by CCK8 and flow cytometry.

Results: Differential expression analysis and clinical testing show that PIK3CG is highly expressed in patients. Prolonged ODG/R exposure increased PIK3CG levels, supressed cell proliferation, and induced apoptosis. KEGG pathway analysis implicated PIK3CG in autophagy pathway. Knockdown of PIK3CG supressed OGD/R-induced reductions in cell proliferation and OGD/R-induced increases in apoptosis and expressions of Beclin 1 and LC3 II. Following OGD/R, AMPK phosphorylation was upregulated while mammalian target of rapamycin (mTOR) phosphorylation was downregulated, indicating AMPK/mTOR autophagy activation. Knockdown of PIK3CG opposed metformin-induced rises in Beclin 1, LC3 II and apoptosis along with decreases in proliferation.

Conclusion: PIK3CG knockdown protects neuronal cells by inhibiting AMPK/mTOR autophagy pathway and further inhibiting autophagy.