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

Yuan,Jiang; Zeng,Lei; Sun,Yanpeng; Wang,Na; Sun,Qiang; Cheng,Zhaohui; Wang,Yunfu

doi:10.3892/mmr.2018.9265

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

Authors:
- Jiang Yuan
- Lei Zeng
- Yanpeng Sun
- Na Wang
- Qiang Sun
- Zhaohui Cheng
- Yunfu Wang
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Affiliations: Department of Neurology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China, Department of Radiology, Ren‑Min Hospital, Hubei University of Medicine, Shiyan, Hubei 442000, P.R. China
Published online on: July 9, 2018 https://doi.org/10.3892/mmr.2018.9265
Pages: 2613-2620
Copyright: © Yuan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

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.

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