SPTLC2 Negatively Regulates Neural Stem Cell Activity and Proliferation via Inhibition of the MEK/ERK Signaling: Insights into the Molecular Mechanisms Underlying Neural Stem Cell Behavior

The utilization of neural stem cells (NSCs) for facilitating neurogenesis and enhance impaired neural functions has drawn people's attention. Serine palmitoyltransferase long chain base subunit 2 (SPTLC2) can induce the apoptosis of neurons, and the mitogen-activated protein kinase (MEK)/extracellular signal-regulated kinase (ERK) pathway is capable of promoting the differentiation and proliferation of NSCs. Nevertheless, the effect and mechanism of SPTLC2 and the MEK/ERK pathway on the activity and proliferation of NSCs remain unclear. In the current study, the expression of SPTLC2 was modulated through plasmid transfection and verified by PCR and western blot. Once the expression of SPTLC2 was changed, the impact on the activity and proliferation of NSCs was observed via cell counting kit (CCK) and 5-ethynyl-2'-deoxyuridine (EdU) staining. To confirm the relationship between SPTLC2 and the MEK/ERK pathway, western blot was employed to observe the correlation of expression changes. To observe whether SPTLC2 worked through MEK/ERK, the activation state of the MEK/ERK pathway was interfered with by Erucin and U0126 reagents. EdU staining and western blot were utilized to verify whether SPTLC2 affected the activity and proliferation of NSCs through MEK/ERK pathway. It was noted that the expression of SPTLC2 could be altered by plasmid transfection at both mRNA and protein levels. Through modifying the expression of SPTLC2, the activity and proliferation of NSCs could be influenced. Meanwhile, we observed that the expression changes of significant proteins in the MEK/ERK pathway were negatively correlated with SPTLC2. Thus, Our results showed that overexpression of SPTLC2 might inhibit the activity and proliferation of NSCs, and conversely, promote the process. The effect of SPTLC2 on NSCs was achieved through the MEK/ERK pathway.