annexin a5 protects sh-sy5y cells against l-glutamate-induced cytotoxicity

Background: l- glutamate- induced neurotoxicity is linked to neuronal loss in neurodegenerative diseases and stroke. annexin a5 (anxa5) is a cytosolic protein that binds calcium in eukaryotic organisms. this study aimed to evaluate the protective effects of a recombinant anxa5 against l-glutamate-induced cell death and mitochondrial dysfunction in sh-sy5y cells.methods: anxa5 was expressed in e. coli and subsequently purified using affinity chromatography. the effect of l-glutamate (0-300 mm) alone or in combination with anxa5 (0-5µg/ml) on the viability of the sh-sy5y cells was assessed using the mtt assay. mitochondrial membrane potential (mmp) dissipation was detected by rhodamine 123 staining and the flow cytometry method. the expressions of bax, bcl-2, and nf-e2-related factor 2 (nrf-2) genes were determined by real-time polymerase chain reaction. graphpad prism 8.0 was used to analyze the data using either one-way anova or the kruskal-wallis test. p<0.05 was considered statistically significant.results: the findings revealed that l-glutamate reduced the cell viability of sh-sy5y cells in a dose-dependent manner (p<0.001) (ic50=165 mm). moreover, treating sh-sy5y cells with 165 mm of l-glutamate increased mmp dissipation, enhanced bax expression, and reduced the expression of bcl-2 and nrf-2, compared to the control group. anxa5 alone had no significant effects. however, it reversed the effects of l-glutamate on cell death, mmp dissipation, and gene expression in the sh-sy5y cells.conclusion: the data suggest that anxa5 can protect sh-sy5y cells against glutamate-induced cell death and mitochondrial dysfunction, indicating its possible protective effect against glutamate-induced neurodegeneration.