PTPN21 protects PC12 cell against oxygen-glucose deprivation by activating cdk5 through ERK1/2 signaling pathway.

PTPN21, a cytosolic non-receptor tyrosine phosphatase isolated from human skeletal muscle, was reported to promote neuronal survival. Nevertheless, it is not clear whether PTPN21 plays a role in hypoxia ischemia-induced neuronal injury. A proper understanding of the PTPN21 mechanism in neuron growth regulation is limited. In this study, we investigated the neuroprotective effects and potential mechanism of PTPN21 on oxygen glucose deprivation (OGD)-injured PC12 cells. The ischemic stroke model of PC12 cells was made by OGD for 2h, after transfection of the PTPN21 siRNA and pcDNA 3.1 PTPN21(+). Cell viability was tested using the MTT and CCK-8 assay. Apoptotic cells were estimated by Annexin V-FITC/PI staining and caspase-3 activity using the Caspase-3 Assay Kit; the PTPN21, cdk5, ERK1/2 and p-ERK1/2 levels were estimated by qRT-PCR and Western blot. We found that the PTPN21 markedly increased cell viability, inhibited apoptosis. We also found that PTPN21 inhibited caspase-3 activity and down-regulating the Bax/Bcl-2 ratio. Furthermore, the expression of cdk5 protein was up-regulated by PTPN21 by activating ERK1/2 signaling pathway. Finally, our results showed that cdk5 siRNA or ERK1/2 signaling inhibitor PD98059 attenuated the accelerative effect of pcDNA3.1 PTPN21(+) on cell proliferation and apoptosis in PC12 cells. In short, it appears that PTPN21 may protect the PC12 from ischemia injury by upregulating cdk5 via ERK1/2 signaling pathway.