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Lipoxin A4 Activates Nrf2 Pathway and Ameliorates Cell Damage in Cultured Cortical Astrocytes Exposed to Oxygen-Glucose Deprivation/Reperfusion Insults

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Abstract

Lipoxin A4 (LXA4), a potent antioxidant and anti-inflammation mediator, protects brains against cerebral ischemia/reperfusion (I/R) injury in vivo. However, few reports concern its function on astrocytes during cerebral I/R injury. The pathogenesis of cerebral I/R injury involves oxidative stress caused by reactive oxygen species (ROS). Upregulation of nuclear factor erythroid 2-related factor 2 (Nrf2) is generally considered to reduce oxidative stress. Nrf2 can induce heme oxygenase-1 (HO-1) expression and glutathione (GSH) release to combat increased oxidative stress. We investigated the effects of LXA4 on astrocytic cell damage, the production of ROS, and Nrf2 pathway, especially on HO-1 expression and GSH release in cultured cortical astrocytes exposed to oxygen-glucose deprivation (OGD)/recovery (OGDR) insults. Primary astrocytes were subjected to a 4-h OGD, followed by 8-h recovery. Cell viability, the production of ROS, and GSH release were measured. Furthermore, Nrf2, HO-1, and p62 expression levels were determined by Western blot. Moreover, Nrf2 location was studied by immunofluorescence staining. Treatment of LXA4 attenuates OGDR-induced cell damage and the production of ROS in a concentration-related manner. LXA4 induced Nrf2 expression and its nuclear translocation, as well as HO-1 expression and GSH release. Moreover, LXA4 induced the excess p62 accumulation. These results indicate that LXA4 can effectively protect against OGDR-induced cell damage in astrocytes, and activation of Nrf2 pathway to reduce oxidative stress may be involved in its protective effects. p62 accumulation induced by LXA4 may be closely related to Nrf2 activation.

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Acknowledgments

This study was supported by the grants from the Natural Science Foundation of China (81100867) and the Wuhan City Outstanding Youth Fund (201150431138).

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Authors and Affiliations

  1. Department of Neurology, Wuhan General Hospital of Guangzhou Command PLA, No. 627, Wuluo Road, Wuhan, 430070, China

    Le Wu, Hong-Hua Li & Qiang Wu

  2. Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan, 430030, China

    Sen Miao, Ping Wu & Du-Yun Ye

  3. Department of Anatomy, Tongji Medical College, Huazhong University of Science and Technology, No. 13, Hangkong Road, Wuhan, 430030, China

    Zi-Jian Liu

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  1. Le Wu
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Correspondence to Hong-Hua Li.

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Wu, L., Li, HH., Wu, Q. et al. Lipoxin A4 Activates Nrf2 Pathway and Ameliorates Cell Damage in Cultured Cortical Astrocytes Exposed to Oxygen-Glucose Deprivation/Reperfusion Insults. J Mol Neurosci 56, 848–857 (2015). https://doi.org/10.1007/s12031-015-0525-6

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  • DOI: https://doi.org/10.1007/s12031-015-0525-6

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