1, 5-Dicaffeoylquinic acid-mediated glutathione synthesis through activation of Nrf2 protects against OGD/reperfusion-induced oxidative stress in astrocytes.
Oxidative stress plays an important role in pathological processes of cerebral ischemia followed by reperfusion. The effect of 1, 5-dicaffeoylquinic acid (1, 5-diCQA) on primary culture rat cortical astrocytes induced by oxygen and glucose deprivation (OGD)/reperfusion was evaluated in this study. Appropriate concentration of 1, 5-diCQA pretreatment significantly suppressed cell death, reduced the production of reactive oxygen species, prevented glutathione (GSH) depletion, increased the activity of glutamate-cysteine ligase (GCL), and triggered Nrf2 nuclear translocation in astrocytes induced by 4h of OGD and 20 h of reperfusion. Interestingly, these protective effects were greatly attenuated in Nrf2 siRNA-transfected cells. We conclude that 1, 5-diCQA has antioxidant signaling properties that upregulate GSH synthesis by stimulating the Nrf2 pathway in astrocytes and protects them from cell death in an in vitro model of ischemia/reperfusion.
Cao
Xu
X
Department of Neurology, Second Clinical College, Jinan University, Shenzhen, 518020, People's Republic of China.
Xiao
Haibing
H
Zhang
Ying
Y
Zou
Liangyu
L
Chu
Yinghao
Y
Chu
Xiaofan
X
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D000860:Hypoxia / Q000188:drug therapy / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015424:Reperfusion / Q000379:methods; D014162:Transfection / Q000379:methods
D051267:NF-E2-Related Factor 2; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; C472707:caffeoylquinic acid; D011801:Quinic Acid; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione