The Effect of on Regulating Mitochondrial Dysfunction in Ischemic Stroke.

Background: Ischemic stroke is an acute cerebrovascular disease with high mortality rates and poor prognoses. The influence of ischemic stroke includes a heavy economic burden to patients and society, making the exploration of new therapeutic targets for preventing and treating ischemic stroke urgent. This study aimed to explore the effect of phosphoglycerate mutase family member 5 () on oxidative stress and mitochondrial dysfunction in ischemic stroke.

Methods: The model of ischemic neuronal brain injury was established through culturing purchased human neuroblastoma cells (SH-SY5Y) by oxygen-glucose deprivation/reoxygenation (OGD/R). There were six experimental groups, including the OGD/R model group (SH-cells of OGD/R model), OE-NC group (cells of OGD/R model transfected with scramble cDNA), OE- group (cells of OGD/R model transfected with full-length sequence of ), si-NC group (cells of OGD/R model transfected with negative control small interference (si)RNA), si- group (cells of OGD/R model transfected with siRNA for knockdown), and a control group (cells cultured normally). Cell counting kit-8 (CCK-8) and flow cytometry were used to determine the activity and apoptosis of cells. Subsequently, the effects of expression on oxidative stress and mitochondrial dysfunction were analyzed. Mitochondrial morphology was observed by transmission electron microscopy (TEM), and mitochondrial membrane potential (MMP) was determined by JC-1 fluorescent probe. The levels of reactive oxygen species (ROS) were measured by flow cytometry, and levels of malondialdehyde (MDA) and superoxide dismutase (SOD) were measured by enzyme-linked immunosorbent assay (ELISA) assay. The expression of light chain (LC)3-II/I and autophagy-related gene 5 (ATG5) proteins were measured, and the regulation of expression on -induced putative protein kinase 1 ()/ pathway was also explored.

Results: overexpression in OGD/R cells decreased the cell viability ( < 0.001) while increasing cell apoptosis ( < 0.01) compared to the OGD/R group. Inhibition of expression reversed the decreased cell viability ( < 0.001) and the increased cell apoptosis ( < 0.01). The JC-1 fluorescence showed that OGD/R treatment reduced mitochondrial membrane potential ( < 0.001) and TEM showed an obvious increase in phagosomes. In addition, OGD/R treatment enhanced oxidative stress (increased ROS, < 0.01; increased MDA, < 0.001; decreased SOD, < 0.001), which could be further enhanced by overexpression of (ROS, < 0.001; MDA, < 0.001; SOD, < 0.001) while reversed by the inhibition of (ROS, < 0.01; MDA, < 0.001; SOD, < 0.001). The OGD/R-activated / pathway was inhibited by the knockdown of ( < 0.01) but promoted by the overexpression of ( < 0.05).

Conclusions: stimulates oxidative stress and impairs mitochondrial function in ischemic stroke, and regulates the / signaling pathway. Therefore, is likely to be a target for the therapy of ischemic stroke.