The Protective Effect of Aromatase on NSC-34 Cells with Stably Expressed hSOD1-G93A. (15th July 2019)

• Record Type: Journal Article
• Authors: Yan, Lina; Qi, Weijing; Liu, Yaling; Zhou, Fuling; Wang, Yafei; Bai, Lin; Zhou, Xiaomeng; Sun, Can; Nie, Xiangyu; Duan, Shiru; Ran, Jina; Chen, Juan; Ji, Yingxiao; Liu, Yakun; Li, Zhongyao; Li, Yuanyuan; Wang, Qingxin
• Is Part Of: Neuroscience. Volume 411(2019)
• Page Start: 37
• Page End: 46
• Publication Date: 2019-07-15
• Subjects: ALS amyotrophic lateral sclerosis -- SOD1 superoxide dismutase -- hSOD1-G93A cells NSC-34 cells with stably expressed hSOD1-G93A -- ORF pen reading frame -- ShRNA short hairpin RNA -- ER-α estrogen receptor α -- ORF open reading frame -- E2 estradiol -- ER-β estrogen receptor-β -- GPR30 G protein-coupled receptor 30 -- HRT hormone replacement therapy -- TEM transmission electron microscopy -- RFP red fluorescent protein -- CCK-8 Cell Counting Kit-8 -- LDH lactic acid dehydrogenase -- RT-PCR real-time polymerase chain reaction -- SDS sodium dodecyl sulfate -- Bax Bcl-2-associated X protein -- Bcl-2 B-cell lymphoma-2 -- LSD least significant difference -- GFP green fluorescent protein -- RFP red fluorescent protein -- ARKO aromatase knockout; amyotrophic lateral sclerosis -- aromatase -- anti-apoptosis -- estrogen receptors -- hSOD1-G93A; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.05.022
• Languages: English
• ISSNs: 0306-4522

Abstract

Abstract: As an adult-onset neurodegenerative disease, amyotrophic lateral sclerosis (ALS) results in progressive muscular atrophy and paralysis. However, the mechanism of ALS has not yet been elucidated, and no cure has been found. Research has revealed that a mutation of the Cu/Zn superoxide dismutase (SOD1) gene is linked to familial ALS and that potential sex discrepancies exist in ALS incidence. Here, NSC-34 cells stably expressing hSOD1-G93A (hSOD1-G93A cells) were transiently transfected with Cyp19a1 mouse open reading frame (ORF) cDNA or a short hairpin RNA (ShRNA) plasmid. Overexpression of aromatase resulting from Cyp19a1 mouse ORF cDNA plasmid transfection enhanced cell proliferation and reduced cell damage in hSOD1-G93A cells. This protective effect occurred through anti-apoptotic pathways related to estrogen receptor-alpha (ER-α) activation. Meanwhile, knockdown of aromatase with Cyp19a1 ShRNA plasmid transfection reduced cell proliferation, increased cell damage, promoted apoptosis, and decreased ER-α expression in hSOD1-G93A cells, and the induced apoptotic effects could be reversed by estradiol (E2). In brief, the results of our study suggest that aromatase plays a neuroprotective role against apoptosis in hSOD1-G93A cells by activating ER-α and may become a new intervention target for ALS treatment. Highlights: Aromatase played a neuroprotective role through an anti-apoptosis mechanism in hSOD1-G93A cells. E2 reversed the apoptotic effect of aromatase knockdown. The anti-apoptotic effect of aromatase was related to ER-α activation.