Nur77 exacerbates PC12 cellular injury in vitro by aggravating mitochondrial impairment and endoplasmic reticulum stress

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dc.creatorGao, Huimin
dc.creatorChen, Zhaoyu
dc.creatorFu, Yongmei
dc.creatorYang, Xiaoyan
dc.creatorWeng, Ruihui
dc.creatorWang, Rui
dc.creatorLu, Jianjun
dc.creatorPan, Mengqiu
dc.creatorJin, Kunlin
dc.creatorMcElroy, Chris
dc.creatorTang, Beisha
dc.creatorXia, Ying
dc.creatorWang, Qing
dc.creator.orcid0000-0002-1336-348X (Jin, Kunlin)
dc.date.accessioned2022-09-09T14:08:42Z
dc.date.available2022-09-09T14:08:42Z
dc.date.issued2016-09-29
dc.description.abstractThe nuclear orphan receptor, Nur77 plays important roles in neuroimflammation, apoptosis, and dopaminergic neurodegeneration. We conducted a further mechanistic investigation into the association of Nur77 with cell death. Cytosporone B (Csn-B), an agonist for Nur77, and Nur77 knockdown were adopted in the 6-hydroxydopamine (OHDA)-lesioned PC12 cells to investigate the mechanisms underlying Nur77-mediated injury. The 6-OHDA incubation caused Nur77 translocation from the nucleus to cytosol and Endoplasm reticulum (ER) and induced co-localization of Tom20/Nur77 and Protein Disulfide Isomerase (PDI)/Nur77. Nur77 activation further decreased cell viability, aggravated intracellular LDH release, intracellular Ca(2+), ROS levels, apoptosis, ER tress and, mitochondrial transmembrane potential (DeltaPsim) decline. In addition, Nur77 activation significantly enhanced the efficiency of autophagy as indicated by an up-regulation of Beclin-1/LC-3 and downregulation of p62, and aggravated mitochondrial dysfunctions and ER stress as shown by increased HSP60/Cytochrome C (Cyt C) and CHOP-ATF3 levels respectively. These changes could be partially reversed by Nur77 knockdown. Moreover, Nur77 activation upregulated PINK1 and downregulated Parkin levels. We conclude that Nur77 exacerbates PC12 cell death at least partially by aggravating the mitochondrial impairment and ER stress and enhancing autophagy. We propose that Nur77 is likely a critical target in the PD therapy.
dc.description.sponsorshipThis work was supported by the National Natural Science Foundation of China (Grant No. 81271427, 81471291), Science and Technology Program of Guangdong of China (2016A050502019), Natural Science Foundations of Guangdong of China (2014A020212068), Guangdong Province Key Laboratory of Brain Function and Disease Foundation, and Scientific Research Foundation of Guangzhou (Grant No. 2014J4100210) to Q.W.
dc.identifier.citationGao, H., Chen, Z., Fu, Y., Yang, X., Weng, R., Wang, R., Lu, J., Pan, M., Jin, K., McElroy, C., Tang, B., Xia, Y., & Wang, Q. (2016). Nur77 exacerbates PC12 cellular injury in vitro by aggravating mitochondrial impairment and endoplasmic reticulum stress. Scientific reports, 6, 34403. https://doi.org/10.1038/srep34403
dc.identifier.issn2045-2322
dc.identifier.urihttps://hdl.handle.net/20.500.12503/31705
dc.identifier.volume6
dc.publisherSpringer Nature
dc.relation.urihttps://doi.org/10.1038/srep34403
dc.rights.holder© The Author(s) 2016
dc.rights.licenseAttribution 4.0 International (CC BY 4.0)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceScientific Reports
dc.titleNur77 exacerbates PC12 cellular injury in vitro by aggravating mitochondrial impairment and endoplasmic reticulum stress
dc.typeArticle
dc.type.materialtext

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