Pretreatment with Sodium Phenylbutyrate Alleviates Cerebral Ischemia/Reperfusion Injury by Upregulating DJ-1 Protein

Frontiers in Neurology

Da-Yun Feng¹  Rui-Xin Yang¹  Fang-Fang Lu¹  Jie Lei¹  Lu Huang¹  Tie-Jian Nie¹  Yu-Qian Li¹  Bo-Dong Wang¹  Chen Li¹  Li Gao¹  Gang Zhu¹  Guo-Dong Gao¹  Tao Li² 

[1] Department of Neurosurgery, Tangdu Hospital, The Fourth Military Medical University, Xi’an, China;Research Center of Traditional Chinese Medicine, Xijing Hospital, The Fourth Military Medical University, Xi’an, China;

关键词: DJ-1;    ischemia/reperfusion injury;    mitochondrial function;    neuroprotection;    sodium phenylbutyrate;    reactive oxygen species;   

DOI  :  10.3389/fneur.2017.00256

来源: DOAJ

【 摘 要 】

Oxidative stress and mitochondrial dysfunction play critical roles in ischemia/reperfusion (I/R) injury. DJ-1 is an endogenous antioxidant that attenuates oxidative stress and maintains mitochondrial function, likely acting as a protector of I/R injury. In the present study, we explored the protective effect of a possible DJ-1 agonist, sodium phenylbutyrate (SPB), against I/R injury by protecting mitochondrial dysfunction via the upregulation of DJ-1 protein. Pretreatment with SPB upregulated the DJ-1 protein level and rescued the I/R injury-induced DJ-1 decrease about 50% both in vivo and in vitro. SPB also improved cellular viability and mitochondrial function and alleviated neuronal apoptosis both in cell and animal models; these effects of SPB were abolished by DJ-1 knockdown with siRNA. Furthermore, SPB improved the survival rate about 20% and neurological functions, as well as reduced about 50% of the infarct volume and brain edema, of middle cerebral artery occlusion mice 23 h after reperfusion. Therefore, our findings demonstrate that preconditioning of SPB possesses a neuroprotective effect against cerebral I/R injury by protecting mitochondrial function dependent on the DJ-1 upregulation, suggesting that DJ-1 is a potential therapeutic target for clinical ischemic stroke.

【 授权许可】

Unknown