Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences
Abstract
:1. Introduction
2. Transcriptomics and the NF-κB Pathway
3. Effects of Microgravity on NF-κB in the Immune System
4. Effects of Microgravity on NF-κB in Muscle
5. Effects of Microgravity on NF-κB in Bone
6. Effects of Microgravity on NF-κB in Cardiovascular System
7. Effects of Microgravity on NF-κB in Brain
8. Effects of Space Radiation Exposure on NF-κB
9. Conclusions
Acknowledgments
Conflicts of Interest
References
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Cells/Organism | Type of Microgravity | Type of Analysis | Length of Exposure | Result | Author |
---|---|---|---|---|---|
Cell Line | |||||
Rat cardiac cells (H9c2) | RWV | Western blot; ELISA on nuclear lysates | 3 h | Increased NF-κB p65 DNA binding activity | Kwon et al. [25] |
Human lymphoblastoid cells (TK6) | RWV | Microarray; PCR array on whole cell lysates | 72 h | Differential expression profile of genes and miRNAs identifying activation of the NF-κB pathway | Mangala et al. [26] |
Activated human T cells | ISS | Microarray on whole cell lysates | 1.5 h | Suppressed expression of cREL/NF-κB gene targets | Chang et al. [27] |
Activated human T cells | RPM | RT-PCR on whole cell lysates | 4 h | Suppressed expression of NF-κB gene targets | Boonyaratnakornkit et al. [28] |
Human Jurkat T cells | RWV | Western blot on nuclear lysates | 5 min | Decreased translocation of NF-κB p65 protein | Paulsen et al. [29] |
Human fibroblasts (AG1522) | ISS | Microarray; PCR array on whole cell lysates | 72 h | Differential expression profile of genes and miRNAs identifying activation of the NF-κB pathway | Zhang et al. [30] |
Human Thyroid cancer cells (FTC-133) | RPM | Microarray; Western blot on whole cell lysates | 24 h | Increased NF-κB p65 protein level | Grosse et al. [31] |
Human Study/Mouse Cells | |||||
Human muscle tissue | Bed-rest | RT-PCR; Western blot on tissue sample | 7 days | Increased expression of NFKB1, No change in total and phosphorylated NF-κB p65 protein level | Drummond et al. [32] |
Human PBMCs; Murine monocyte/macrophage cells (RAW264.7) | RWV for RAW264.7 cells; Space Shuttle for PBMCs | Western blot and ELISA on nuclear lysates for RAW264.7 cells; Immunocytochemical method for PBMCs | 24 h for RAW264.7 cells; 12–16 days for PBMCs | Increased NF-κB p65 DNA binding activity and increased p65 protein level in RAW264.7 cells; Increased NF-κB p65 protein level after spaceflight; Omega-3 fatty acids or eicosapentaenoic acid reduced NF-κB p65 protein level | Zwart et al. [33] |
Mouse Study | |||||
Mouse Gastrocnemius (C57BL/6) | STS-108; HU | Microarray; RT-PCR on tissue sample | 11 days 19 h | Increased expression of Nfkbia/Iκbα | Allen et al. [34] |
Moue spleen (C57BL/6) | STS-135 | PCR array on tissue sample | 13 days | Suppressed expression of Nfκb1 | Gridley et al. [35] |
WT and Nfkb1−/− or Bcl-3−/− mouse gastrocnemius and plantaris muscles (B6129PF2/) | HU | Microarray; RT-PCR on tissue sample | 10 days | Reduced muscle atrophy in Nfkb1−/− or Bcl-3−/− mice; Increased expression of NF-κB gene targets in WT mice | Wu et al. [36] |
WT and Nfkb1−/− mouse bone (C57BL/6) | HU | µCT on tibias and femurs bone mass; Western blot on tissue sample | 2 weeks | Reduced bone loss in Nfkb1−/− mice in comparison to WT, Increased NF-κB p50 protein level in WT HU group | Nakamura et al. [37] |
Mouse brain (BALB/c) | HU | EMSA on nuclear lysates | 7 days | Increased NF-κB DNA binding activity | Wise et al. [38] |
Cells/Organism | Radiation Type and Quality | Dose/Dose Rate Range | Method | Result | Reference |
---|---|---|---|---|---|
Cell Line | |||||
Human embryonic kidney cells (HEK 293) | C (34 keV/µm) Ne (91 keV/µm); Ar (272 keV/µm); Ni (906 keV/µm); Pb (9674 keV/µm) | 0.1–60 Gy ~1 Gy/min | Fluorescence d2EGFP reporter gene assay | RBE for NF-κB dependent d2EGFP expression varies by particle types with peak RBE = 8.9 | Hellweg et al. [39] |
Human monocytes (MM6) | Fe | 0.2–1.4 Gy 1 Gy/min | EMSA on nuclear lysates | NF-κB DNA binding activity increased in a dose and time dependent manner | Natarajan et al. [40] |
Human embryonic kidney cells (HEK 293) | Ar (230 keV/µm) | 0.2–30 Gy | Fluorescence d2EGFP reporter gene assay | Increased NF-κB dependent d2EGFP expression in a dose and time dependent manner | Baumstark-Khan et al. [41] |
Human embryonic kidney cells (HEK 293) | C (33 and 73 keV/µm) | 0.2–20 Gy ~1 Gy/min | Fluorescence d2EGFP reporter gene assay | NF-κB dependent d2EGFP expression was comparable to X-rays | Hellweg et al. [42] |
Chinese hamster cells (V79) | O | 1 Gy | Western blot on whole cell lysates | Decreased NF-κB p65 level at 30 min post irradiation, but the level recovered at longer time points | Mitra et al. [43] |
Mouse Study | |||||
Mouse bone marrow (BALB/cJ) | Proton (0.7 keV/µm) | 1 Gy 5 and 10 mGy/min | ELISA on nuclear lysates | NF-κB p65 DNA binding activity was both dose rate and time dependent | Rithidech et al. [44] |
Mouse spleen T cells (C57BL/6) | SPE protons | 1.7 Gy delivered over 36 h | ELISA on whole cell lysates | Increased total and phosphorylated form of NF-κB p65 | Rizvi et. al. [45] |
Mouse heart and bone marrow (CBA/CaJ) | Si (77 keV/µm) | 0.1–0.5 Gy 10 mGy/min in two fractionations with 15 days apart | ELISA on nuclear lysates | Increased NF-κB p65 DNA binding activity up to 6 months post irradiation | Tungjai et al. [46] |
Mouse liver (CBA/CaJ) | Ti (107 keV/µm) | 0.1–0.5 Gy 0.01 Gy/min | ELISA on nuclear lysates | Increased level of NF-κB p65 DNA binding activity up to 6 months post irradiation | Jangiam et al. [47] |
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Zhang, Y.; Moreno-Villanueva, M.; Krieger, S.; Ramesh, G.T.; Neelam, S.; Wu, H. Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences. Int. J. Mol. Sci. 2017, 18, 1166. https://doi.org/10.3390/ijms18061166
Zhang Y, Moreno-Villanueva M, Krieger S, Ramesh GT, Neelam S, Wu H. Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences. International Journal of Molecular Sciences. 2017; 18(6):1166. https://doi.org/10.3390/ijms18061166
Chicago/Turabian StyleZhang, Ye, Maria Moreno-Villanueva, Stephanie Krieger, Govindarajan T. Ramesh, Srujana Neelam, and Honglu Wu. 2017. "Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences" International Journal of Molecular Sciences 18, no. 6: 1166. https://doi.org/10.3390/ijms18061166