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Protocatechualdehyde Protects Against Cerebral Ischemia-Reperfusion-Induced Oxidative Injury Via Protein Kinase Cε/Nrf2/HO-1 Pathway

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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.

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Acknowledgments

This present study was supported by grants from the National Natural Science Foundation of China (No. 81403134). We thank our colleagues from the Department of Neurology for their constructive advices on our experiments.

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    Authors and Affiliations

    1. Department of Pharmacy, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

      Chao Guo, Jialin Duan, Na Jia, Yanrong Zhu, Yi Ding, Yue Guan, Guo Wei, Ying Yin, Miaomaio Xi & Aidong Wen

    2. Department of Anesthesiology, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, People’s Republic of China

      Shiquan Wang

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    1. Chao Guo
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    Experimental protocols were approved by the Ethics Committee for Animal Experimentation of the Fourth Military Medical University (Xi’an, China).

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    Chao Guo, Shiquan Wang, Jialin Duan and Na Jia contributed equally to this work.

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    Guo, C., Wang, S., Duan, J. et al. Protocatechualdehyde Protects Against Cerebral Ischemia-Reperfusion-Induced Oxidative Injury Via Protein Kinase Cε/Nrf2/HO-1 Pathway. Mol Neurobiol 54, 833–845 (2017). https://doi.org/10.1007/s12035-016-9690-z

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