Increasing expression of dual-specificity phosphatase 12 mitigates oxygen-glucose deprivation/reoxygenation-induced neuronal apoptosis and inflammation through inactivation of the ASK1-JNK/p38 MAPK pathway

Abstract

Dual-specificity phosphatase 12 (DUSP12) is abnormally expressed under various pathological conditions and plays a crucial role in the pathological progression of disorders. However, the role of DUSP12 in cerebral ischaemia/reperfusion injury has not yet been investigated. This study explored the possible link between DUSP12 and cerebral ischaemia/reperfusion injury using an oxygen-glucose deprivation/reoxygenation (OGD/R) model. Marked decreases in DUSP12 levels have been observed in cultured neurons exposed to OGD/R. DUSP12-overexpressed neurons were resistant to OGD/R-induced apoptosis and inflammation, whereas DUSP12-deficient neurons were vulnerable to OGD/R-evoked injuries. Further investigation revealed that DUSP12 overexpression or deficiency affects the phosphorylation of apoptosis signal-regulating kinase 1 (ASK1), c-Jun NH2-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) in neurons under OGD/R conditions. Moreover, blockade of ASK1 diminished the regulatory effect of DUSP12 deficiency on JNK and p38 MAPK activation. In addition, DUSP12-deficiency-elicited effects exacerbating neuronal OGD/R injury were reversed by ASK1 blockade. In summary, DUSP12 protects against neuronal OGD/R injury by reducing apoptosis and inflammation through inactivation of the ASK1-JNK/p38 MAPK pathway. These findings imply a neuroprotective function for DUSP12 in cerebral ischaemia/reperfusion injury.

Keywords:

• ASK1
• cerebral ischaemia/reperfusion injury
• DUSP12
• oxygen-glucose deprivation/reoxygenation
• JNK
• p38

Acknowledgments

Not applicable.

Authors’ contributions

Jiaxuan He designed the study, performed the experiments, and wrote the manuscript. Siyuan Li, Yunpeng Teng, Hongfei Xiong, and Zhuang Wang performed experiments. Xiaoyao Han and Wei Gong performed data analysis and provided technical support. Ya Gao contributed to the conceptualization and reviewed the manuscript. All authors have read and approved the final version of the manuscript.

Disclosure statement

The authors report there are no competing interests to declare.

Data availability statement

The datasets used in this study are available from the corresponding author upon reasonable request.

Additional information

Funding

Not applicable.