title: Protocatechualdehyde Protects Against Cerebral Ischemia-Reperfusion-Induced Oxidative Injury Via Protein Kinase Cε/Nrf2/HO-1 Pathway.
abstract: Oxidative stress is closely related to the pathogenesis of ischemic stroke. Protocatechualdehyde (PCA) is a phenolic acid compound that has the putative antioxidant activities. The present study was aimed to investigate the molecular mechanisms involved in the antioxidative effect of PCA against cerebral ischemia/reperfusion (I/R) injury. The experiment stroke model was produced in Sprague-Dawley rats via middle cerebral artery occlusion (MCAO). To model ischemia-like conditions in vitro, differentiated SH-SY5Y cells were exposed to transient oxygen and glucose deprivation (OGD). Treatment with PCA significantly improved neurologic score, reduced infarct volume and necrotic neurons, and also decreased reactive oxygen species (ROS) production, 4-hydroxynonenal (4-HNE), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) contents at 24 h after reperfusion. Meanwhile, PCA significantly increased the transcription nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) expressions in the ischemic cerebral cortex as shown by immunofluorescence staining and Western blot analysis. In vitro experiment showed that PCA protected differentiated SH-SY5Y cells against OGD-induced injury. Likewise, PCA also increased markedly the Nrf2 and HO-1 expressions in a dose-dependent manner. The neuroprotection effect of PCA was abolished by knockdown of Nrf2 and HO-1. Moreover, knockdown of protein kinase Cε (PKCε) also blocked PCA-induced Nfr2 nuclear translocation, HO-1 expression, and neuroprotection. Taken together, these results provide evidences that PCA can protect against cerebral ischemia-reperfusion-induced oxidative injury, and the neuroprotective effect involves the PKCε/Nrf2/HO-1 pathway.
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Chao
authors.initials: C
authors.lastname: Guo
authors.affiliation: Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Shiquan
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Jialin
authors.initials: J
authors.lastname: Duan
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Na
authors.initials: N
authors.lastname: Jia
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Guan
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Guo
authors.initials: G
authors.lastname: Wei
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Yin
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China. handsomfish@aliyun.com.cn.
authors.forename: Miaomaio
authors.initials: M
authors.lastname: Xi
authors.affiliation: Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi'an, 710032, People's Republic of China. adwen_2015@sina.cn.
authors.forename: Aidong
authors.initials: A
authors.lastname: Wen
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology / Q000627:therapeutic use; D001547:Benzaldehydes / Q000494:pharmacology / Q000627:therapeutic use*; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D002396:Catechols / Q000494:pharmacology / Q000627:therapeutic use*; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000096:biosynthesis*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051744:Protein Kinase C-epsilon / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000517:prevention & control; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D000925:Anticoagulants; D001547:Benzaldehydes; D002396:Catechols; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; C495637:Nfe2l2 protein, rat; C005581:protocatechualdehyde; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D051744:Protein Kinase C-epsilon
keywords: HO-1; Ischemic stroke; Nrf2; Oxidative stress; PKCε