CDC42 Regulates the ERK Pathway to Improve Oxygen-Glucose Deprivation/Reoxygenation-Induced Neural Oxidative Stress and Apoptosis

CDC42 regulates neural morphology, differentiation, and injury and modifies oxidative stress and neural immune infiltration, but its effect on oxygen-glucose deprivation/reoxygenation (OGD/R)-induced neural injury has not been reported. Therefore, this study aimed to investigate the effects of CDC42 overexpression on neural injury and oxidative stress during the OGD/R process. The OGD/R cellular model was established by culturing HT22 cells in glucose-free medium under hypoxic conditions for 2, 4, or 6 h and then transferring them to complete medium and a standard environment for another 24 h. CDC42 and negative control overexpression vectors (oeCDC42 and oeNC) were transfected into HT22 cells; afterwards, PD98059, a specific ERK inhibitor, was added along with or without oeCDC42. CDC42 expression, cell viability, and superoxide dismutase (SOD) activity were reduced, but cell apoptosis and reactive oxygen species (ROS) were elevated after OGD/R induction in a time-dependent manner. oeCDC42 decreased cell apoptosis and ROS and increased SOD activity in OGD/R-induced HT22 cells, but it did not significantly increase cell viability. Moreover, oeCDC42 positively regulated p-ERK and p-c-Fos expression. In addition, PD98059 decreased cell viability and SOD activity but increased cell apoptosis and ROS in OGD/R-induced HT22 cells; moreover, the effects of PD98059 combined with oeCDC42 also showed similar trends compared to oeCDC42 alone regarding the above indexes. CDC42 can ameliorate OGD/R-induced neural oxidative stress and apoptosis by regulating the ERK pathway.