SH2B1 protects against OGD/R-induced apoptosis in PC12 cells via activation of the JAK2/STAT3 signaling pathway

Apoptosis acts as the primary pathogenesis of cerebral ischemia/reperfusion (I/R) injury. Prior studies have revealed the effects of src homology 2 (SH2)B adaptor protein 1 (SH2B1) in myocardial infarction; however, involvement of SH2B1 in cerebral I/R injury and the underlying mechanisms remain to be investigated. In the present study, neural-like PC12 cells underwent 6 h of oxygen-glucose deprivation (OGD) followed by 24 h of reoxygenation (OGD/R). PC12 cells were pre-transfected with an adenovirus encoding for SH2B1 or GFP prior to exposure to OGD/R. Cell viability, LDH release and the apoptotic cascade were investigated. Reverse transcription-quantitative polymerase chain reaction and western blotting were employed to analyze mRNA and protein expression levels, respectively. The results of the present study revealed that OGD/R reduced SH2B1 expression in PC12 cells, accompanied by suppressed cell viability and enhanced cell death. Adenovirus-mediated SH2B1 overexpression, however, resulted in increased viability, reduced LDH release and a reduction in the expression levels of proteins associated with the apoptotic cascade in PC12 cells under the OGD/R condition. A mechanistic explanation may be that the positive effects of SH2B1 on neurons were in part derived from the activation of the JAK2/STAT3 signaling pathway. Furthermore, abolishment of JAK2/STAT3 signaling using a pharmacological inhibitor suppressed the inhibitory effects of SH2B1 under the OGD/R condition. The results of the present study suggested that SH2B1 may protect PC12 cells from OGD/R injury partially by the JAK2/STAT3-dependent inhibition of apoptosis and may provide a novel therapeutic target for the treatment of cerebral I/R injury.