Simulated Microgravity Promotes Cell Apoptosis Through Suppressing Uev1A/TICAM/TRAF/NF-κB-Regulated Anti-Apoptosis and p53/PCNA- and ATM/ATR-Chk1/2-Controlled DNA-Damage Response Pathways

Journal of Cellular Biochemistry
Tuo ZhaoJim Xiang

Abstract

Microgravity has been known to induce cell death. However, its underlying mechanism is less studied. In this study, BL6-10 melanoma cells were cultured in flasks under simulated microgravity (SMG). We examined cell apoptosis, and assessed expression of genes associated with apoptosis and genes regulating apoptosis in cells under SMG. We demonstrate that SMG induces cell morphological changes and microtubule alterations by confocal microscopy, and enhances apoptosis by flow cytometry, which was associated with up- and down-regulation of pro-apoptotic and anti-apoptotic genes, respectively. Moreover, up- and down-regulation of pro-apoptotic (Caspases 3, 7, 8) and anti-apoptotic (Bcl2 and Bnip3) molecules was confirmed by Western blotting analysis. Western blot analysis also indicates that SMG causes inhibition of an apoptosis suppressor, pNF-κB-p65, which is complemented by the predominant localization of NF-κB-p65 in the cytoplasm. SMG also reduces expression of molecules regulating the NF-κB pathway including Uev1A, TICAM, TRAF2, and TRAF6. Interestingly, 10 DNA repair genes are down-regulated in cells exposed to SMG, among which down-regulation of Parp, Ercc8, Rad23, Rad51, and Ku70 was confirmed by Western blotting analysis. ...Continue Reading

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Citations

Oct 13, 2018·Thoracic Cancer·Miao Chen, Songbo Xie
Mar 2, 2019·In Vitro Cellular & Developmental Biology. Animal·Banglian DengJun Chen
Feb 14, 2018·International Journal of Molecular Medicine·Qingbing MengMinqian Zheng
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Jan 21, 2021·International Journal of Molecular Sciences·Noemi MontiMariano Bizzarri
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Dec 16, 2020·International Journal of Molecular Sciences·Binod PrasadMarcus Krüger
May 20, 2021·Stem Cells International·Uğur Topal, Cihan Zamur
Jun 20, 2017·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Yang-Bo GuanYu-Xi Shan

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