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.
摘要：
双特异性磷酸酶12（DUSP12）在各种病理条件下异常表达，在疾病的病理进展中起着至关重要的作用。然而,尚未研究DUSP12在脑缺血/再灌注损伤中的作用.本研究使用氧糖剥夺/复氧（OGD/R）模型探索了DUSP12与脑缺血/再灌注损伤之间的可能联系。在暴露于OGD/R的培养神经元中观察到DUSP12水平显着降低。DUSP12过表达的神经元对OGD/R诱导的细胞凋亡和炎症具有抗性，而DUSP12缺陷的神经元容易受到OGD/R诱发的损伤。进一步研究发现DUSP12过表达或缺失影响凋亡信号调节激酶1(ASK1)的磷酸化,c-JunNH2末端激酶（JNK），在OGD/R条件下神经元中的p38丝裂原活化蛋白激酶(MAPK)。此外，ASK1的阻断降低了DUSP12缺乏对JNK和p38MAPK激活的调节作用。此外,DUSP12缺乏引起的加重神经元OGD/R损伤的作用被ASK1阻断逆转。总之,DUSP12通过ASK1-JNK/p38MAPK通路的失活减少凋亡和炎症，从而保护神经元OGD/R损伤。这些发现暗示DUSP12在脑缺血/再灌注损伤中具有神经保护功能。
