Nucleoredoxin Knockdown in SH-SY5Y Cells Promotes Cell Renewal

Nucleoredoxin (NXN) is a redox regulator of Disheveled and thereby of WNT signaling. Deficiency in mice leads to cranial dysmorphisms and defects of heart, brain, and bone, suggesting defects of cell fate determination. We used shRNA-mediated knockdown of NXN in SH-SY5Y neuroblastoma cells to study...

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Main Authors: Lucie Valek, Irmgard Tegeder
Format: Article
Language:English
Published: MDPI AG 2021-03-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/10/3/449
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author Lucie Valek
Irmgard Tegeder
author_facet Lucie Valek
Irmgard Tegeder
author_sort Lucie Valek
collection DOAJ
description Nucleoredoxin (NXN) is a redox regulator of Disheveled and thereby of WNT signaling. Deficiency in mice leads to cranial dysmorphisms and defects of heart, brain, and bone, suggesting defects of cell fate determination. We used shRNA-mediated knockdown of NXN in SH-SY5Y neuroblastoma cells to study its impact on neuronal cells. We expected that shNXN cells would easily succumb to redox stress, but there were no differences in viability on stimulation with hydrogen peroxide. Instead, the proliferation of naïve shNXN cells was increased with a higher rate of mitotic cells in cell cycle analyses. In addition, basal respiratory rates were higher, whereas the relative change in oxygen consumption upon mitochondrial stressors was similar to control cells. shNXN cells had an increased expression of redox-sensitive heat shock proteins, Hsc70/HSPA8 and HSP90, and autophagy markers suggested an increase in autophagosome formation upon stimulation with bafilomycin and higher flux under low dose rapamycin. A high rate of self-renewal, autophagy, and upregulation of redox-sensitive chaperones appears to be an attractive anti-aging combination if it were to occur in neurons in vivo for which SH-SY5Y cells are a model.
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spelling doaj.art-165823b9e22640278c8f442b5704ccf02023-11-21T10:24:45ZengMDPI AGAntioxidants2076-39212021-03-0110344910.3390/antiox10030449Nucleoredoxin Knockdown in SH-SY5Y Cells Promotes Cell RenewalLucie Valek0Irmgard Tegeder1Institute of Clinical Pharmacology, Medical Faculty, Goethe-University, 60590 Frankfurt, GermanyInstitute of Clinical Pharmacology, Medical Faculty, Goethe-University, 60590 Frankfurt, GermanyNucleoredoxin (NXN) is a redox regulator of Disheveled and thereby of WNT signaling. Deficiency in mice leads to cranial dysmorphisms and defects of heart, brain, and bone, suggesting defects of cell fate determination. We used shRNA-mediated knockdown of NXN in SH-SY5Y neuroblastoma cells to study its impact on neuronal cells. We expected that shNXN cells would easily succumb to redox stress, but there were no differences in viability on stimulation with hydrogen peroxide. Instead, the proliferation of naïve shNXN cells was increased with a higher rate of mitotic cells in cell cycle analyses. In addition, basal respiratory rates were higher, whereas the relative change in oxygen consumption upon mitochondrial stressors was similar to control cells. shNXN cells had an increased expression of redox-sensitive heat shock proteins, Hsc70/HSPA8 and HSP90, and autophagy markers suggested an increase in autophagosome formation upon stimulation with bafilomycin and higher flux under low dose rapamycin. A high rate of self-renewal, autophagy, and upregulation of redox-sensitive chaperones appears to be an attractive anti-aging combination if it were to occur in neurons in vivo for which SH-SY5Y cells are a model.https://www.mdpi.com/2076-3921/10/3/449nucleoredoxinSH-SY5Y neuroblastoma cellshydrogen peroxidecell cycleautophagychaperone-mediated autophagy
spellingShingle Lucie Valek
Irmgard Tegeder
Nucleoredoxin Knockdown in SH-SY5Y Cells Promotes Cell Renewal
Antioxidants
nucleoredoxin
SH-SY5Y neuroblastoma cells
hydrogen peroxide
cell cycle
autophagy
chaperone-mediated autophagy
title Nucleoredoxin Knockdown in SH-SY5Y Cells Promotes Cell Renewal
title_full Nucleoredoxin Knockdown in SH-SY5Y Cells Promotes Cell Renewal
title_fullStr Nucleoredoxin Knockdown in SH-SY5Y Cells Promotes Cell Renewal
title_full_unstemmed Nucleoredoxin Knockdown in SH-SY5Y Cells Promotes Cell Renewal
title_short Nucleoredoxin Knockdown in SH-SY5Y Cells Promotes Cell Renewal
title_sort nucleoredoxin knockdown in sh sy5y cells promotes cell renewal
topic nucleoredoxin
SH-SY5Y neuroblastoma cells
hydrogen peroxide
cell cycle
autophagy
chaperone-mediated autophagy
url https://www.mdpi.com/2076-3921/10/3/449
work_keys_str_mv AT lucievalek nucleoredoxinknockdowninshsy5ycellspromotescellrenewal
AT irmgardtegeder nucleoredoxinknockdowninshsy5ycellspromotescellrenewal