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PAQR3 protects against oxygen–glucose deprivation/reperfusion-induced injury through the ERK signaling pathway in N2A cells

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Abstract

Cerebral ischemia–reperfusion injury is pivotal in the development of multiple-subcellular organelle and tissue injury after acute ischemic stroke. Recently, the Golgi apparatus (GA) has been shown to be a key subcellular organelle that plays an important role in neuroprotection against oxygen–glucose deprivation/reperfusion (OGD/R) injury. PAQR3, a scaffold protein exclusively localized in the GA, was originally discovered as a potential tumor suppressor protein. PAQR3 acts as a spatial regulator of Raf-1 that binds Raf-1 and sequesters it to the GA, where it negatively modulates the Ras/Raf/MEK/ERK signaling pathway in tumor models. Studies suggest that suppression of the ERK pathway can alleviate OGD/R-induced cell apoptosis. However, whether PAQR3 has potential effects on ischemic stroke and the underlying mechanism(s) remain unexplored. The current study is the first to show that PAQR3 was significantly downregulated in mouse neuroblastoma (N2A) cells upon OGD/R exposure, both at the mRNA and protein levels. Compared to that in controls, the mRNA level of PAQR3 began to decline at 0 h (0 h) after reperfusion, while the protein level began to decline at 4 h. Furthermore, overexpression of PAQR3 reduced OGD/R-induced apoptosis. The mRNA and protein levels of total ERK1 and ERK2 were unaltered, while activated p-ERK1 and p-ERK2 were decreased in N2A cells transfected with a PAQR3 expression vector after OGD for 4 h plus 24 h of reperfusion. Collectively, these data indicated that increased PAQR3 expression protected against OGD/R-induced apoptosis possibly by inhibiting the ERK signaling pathway. Therefore, PAQR3 might be a new attractive target in the treatment of OGD/R insult, and the underlying mechanism will pave the way for its potential experimental and clinical application.

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Authors and Affiliations

  1. Department of Rehabilitation, Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Wenna Peng

  2. Department of Emergency, First Xiangya Hospital, Central South University, Changsha, Hunan, China

    Xiaoye Mo

  3. Colleges of Medicine, Jishou University, Jishou, Hunan, China

    Lihua Li

  4. Department of Intensive Care Unit, Hunan Provincial People’s Hospital, Hunan Normal University, Changsha, Hunan, China

    Tonglin Lu

  5. Department of Neurology, Second Xiangya Hospital, Central South University, Changsha, Hunan, China

    Zhiping Hu

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  1. Wenna Peng
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  2. Xiaoye Mo
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  3. Lihua Li
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  4. Tonglin Lu
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  5. Zhiping Hu
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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by WP. The first draft of the manuscript was written by WP and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Zhiping Hu.

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Peng, W., Mo, X., Li, L. et al. PAQR3 protects against oxygen–glucose deprivation/reperfusion-induced injury through the ERK signaling pathway in N2A cells. J Mol Hist 51, 307–315 (2020). https://doi.org/10.1007/s10735-020-09881-w

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  • DOI: https://doi.org/10.1007/s10735-020-09881-w

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