Summary
Microgravity induces inflammatory responses and modulates immune functions that may increase oxidative stress. Exposure to a microgravity environment induces adverse neurological effects; however, there is little research exploring the etiology of these effects resulting from exposure to such an environment. It is also known that spaceflight is associated with increase in oxidative stress; however, this phenomenon has not been reproduced in land-based simulated microgravity models. In this study, an attempt has been made to show the induction of reactive oxygen species (ROS) in mice brain, using ground-based microgravity simulator. Increased ROS was observed in brain stem and frontal cortex with concomitant decrease in glutathione, on exposing mice to simulated microgravity for 7 d. Oxidative stress-induced activation of nuclear factor-kappaB was observed in all the regions of the brain. Moreover, mitogen-activated protein kinase kinase was phosphorylated equally in all regions of the brain exposed to simulated microgravity. These results suggest that exposure of brain to simulated microgravity can induce expression of certain transcription factors, and these have been earlier argued to be oxidative stress dependent.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Aggarwal, B. B. Nuclear factor-kappaB: the enemy within. Cancer Cell 6:203–208; 2004.
Apel, K.; Hirt, H. Reactive oxygen species, oxidative stress, antioxidants and signal transduction. Annu. Rev. Plant Biol. 56:373–399; 2004.
Baldwin, A., Jr. The transcription factor NF-κB and human disease. J. Clin. Invest. 107:3–6; 2001.
Beaver, J.; Waring, P. A. Decrease in intracellular glutathione concentration precedes the onset of apoptosis in murine thymocytes. Eur. J. Cell Biol. 68:47–54; 1995.
Bradford, M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein dye binding. Anal. Biochem. 72:248–254; 1976.
Chapes, S. K.; Mastro, A. M.; Sonnenfeld, G.; Berry, W. D. Antiorthostatic suspension as model for the effects of spaceflight on the immune system. J. Leukoc. Biol. 54:227–237; 1993.
Collins, T.; Cybulsky, M. NF-κB: pivotal mediator or innocent bystander in atherogenesis? J. Clin. Invest. 107:255–264; 2001.
DeHart, R. L., ed. Fundamentals of aerospace medicine. Philadelphia, PA: Lea & Febiger; 1985; 840.
Felix, K.; Wise, K.; Manna, S. K., et al. Altered cytokine expression in tissue of mice subjected to simulated microgravity. Mol. Cell. Biochem. 266:79–85; 2004.
Felix, M.; Manna, S. K.; Wise, K.; Barr, J.; Ramesh, G. T. Low levels of arsenite activates nuclear factor-kappa B and activator protein-1 in immortalized mesencephalic cells. J. Biochem. Mol. Toxicol. 19:67–77 2005.
Granet, C.; Boutahar, N.; Vico, L.; Alexandre, C.; Lafage-Proust, M. H. MAPK and SRC-kinases control EGR-1 and NF-kappa B inductions by changes in mechanical environment in osteoblasts. Biochem. Biophys. Res. Commun. 284:622–631; 2001.
Guignandon, A.; Lafage-Proust, M.; Usson, Y.; Laroche, N.; Caillot-Augusseau, A.; Alexandre, C.; Vico, L. Cell cycling determines integrinmediated adhesion in osteoblastic ROS 17/2.8 cells exposed to space-related conditions. FASEB J. 15:2036–2038; 2001.
Hirasaka, K.; Nikawa, T.; Yuge, L., et al. Clinorotation prevents differentiation of rat myoblastic L6 cells in association with reduced NF-kappaB signaling. Biochim. Biophys. Acta 1743:130–140; 2005.
Hollander, J.; Gore, M.; Fiebig, R., Mazzeo, R., Ohishi, S.; Ohno, H.; Ji, L. L. Space flight downregulates antioxidant defense systems in rat liver. Free Radic. Biol. Med. 24:385–390; 1998.
Kahwaji, C. I.; Sheibani, S.; Han, S.; Sui, W. O.; Kaka, A. H.; Fathy, T. M.; El-Abbad, N. H.; Purdy, R. E. Evidence that simulated microgravity may alter nonreceptor tyrosine kinase second messenger pathway. Proc. West. Pharmacol. Soc. 43:75–77; 2000.
Kane, D. J.; Sarafian, T. A.; Anton, R.; Hahn, H.; Gralla, E. B.; Valentine, J. S.; Örd, T.; Bredesen, D. E. Bcl-2 inhibition of neuronal death: decreased generation of reactive oxygen species. Science 262:1274–1277; 1993.
Karin, M. The regulation of AP-1 activity by mitogen-activated protein kinases. J. Biol. Chem. 270:16483–16486; 1995.
Kopp, E. B.; Ghosh, S. NF-κB and rel proteins in innate immunity. Adv. Immunol. 58:1–27; 1995.
Kulkarni, A. D.; Yamauchi, K.; Hales, N. H.; Ramesh, V.; Ramesh, G. T.; Sundareasan, A.; Andrassy, A.; Pellis, N. R. Nutrition beyond nutrition: plausibility of immunotrophic nutrition for space travel. Clin. Nutr. 21:231–238; 2002.
Leonard, S. S.; Harris, G. K.; Shi, X. Metal induced oxidative stress and signal transduction. Free Radic. Biol. Med. 37:1921–1942; 2004.
Macho, A.; Hirsch, T.; Marzo, I.; Marchetti, P.; Dallaporta, B.; Susin, S. A.; Zamzami, N.; Kroemer, G. Glutathione depletion is an early and calcium elevation is a late event of thymocyte apoptosis. J. Immunol. 158:4612–4619; 1997.
Manna, S. K.; Ramesh, G. T. Interleukin-8 induces nuclear transcription factor-κB through TRAF6-dependent pathway. J. Biol. Chem. 280:7010–7021; 2005.
Markin, A. A.; Zhuravleva, O. A. Lipid peroxidation and antioxidant defense system in rats after a 14-day space flight in the “Space-2044” space-craft. Aviakosm Ekolog Med. 27:47–50; 1993.
Morey, E.; Sabelman, E.; Turner, R.; Baylink, D. A new rat model simulating some aspects of spaceflight. Physiologist 22:S23-S24; 1979.
Morey-Holton, E.; Globus, R. Hindlimb unloading rodent model: technical aspects. J. Appl. Physiol. 92:1367–1377; 2002.
Mylonas, C.; Kouretas, D.: Lipid peroxidation and tissue damage. In Vivo 13:295–309; 1999.
Nakamura, K.; Kuga, H.; Morisaki, T., Boba, E.; Sato, N.; Mizumoto, K.; Sueishi, K.; Tanoka, M.; Katano, M. Simulated microgravity culture system for a 3D carcinoma tissue model. BioTechniques 33:1068–1070; 2002.
Pastore, A.; Federici, G.; Bertini, E.; Piemonte, F. Analysis of glutathione: implication in redox and detoxification. Clin. Chim. Acta. 333:19–39; 2003.
Pavlović, D.; dOrdević, V.; Kocić, G. A “Cross-Talk” between oxidative stress and re-dox cell signaling. Med. Biol. 9(2):131–137; 2002.
Ramesh, G. T.; Jadhav, A. L.; Palur, G. Contribution of PKC and glutamate in Pb-induced cytotoxicity. Toxicol. Lett. 115:89–98; 2000.
Ramesh, G. T.; Manna, S. K.; Aggarwal, B. B.; Jadhav, A. L. Lead activates nuclear transcription factor kappa B, activator protein-1 and N-terminal c-Jun kinase in pheochromacytoma cells. Toxicol. Appl. Pharmacol. 155:280–286; 1999.
Ramesh, G. T.; Manna, S. K.; Aggarwal, B. B.; Jadhav, A. L. Lead exposure activates nuclear transcription factor kappa B, activator protein-1 and c-Jun N-terminal kinase and caspase in the rat brain. Toxicol. Lett. 123:195–207; 2001.
Ray, C. A.; Vasques, M.; Miller, T. A.; Wilkerson, M. K.; Delp, M. D. Effect of short-term microgravity and long-term hindlimb unloading on rat cardiac mass and function. J. Appl. Physiol. 91:1207–1213; 2001.
Roux, P. P.; Blenis, J.; ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol. Mol. Biol. Rev. 68:320–344; 2004.
Sato, N.; Iwata, S.; Nakamura, K.; Hori, T.; Mori, K.; Yodoi, J. Thiol-mediated redox regulation of apoptosis. Possible roles of cellular thiols other than glutathione in T cell apoptosis. J. Immunol. 154: 3194–3203; 1995.
Schulz, E.; Anter, E.; Keaney, J. E., Jr., Oxidative stress antioxidants and endothelial function. Curr. Med. Chem. 11:1093–1104; 2004.
Sreenivasan, Y.; Sarkar, A.; Manna, S. K. Mechanism of cytosine arabinoside mediated apoptosis: role of Rel A (p65) dephosphorylation. Oncogene 22:4356–4369; 2003.
Stein, T. P.; Schluter, M. D. Excretion of amino acids by humans during space flight. Acta Astronaut 42:205–214; 1998.
Storz, P.; Toker, A. NF-kappa B signalling—an alternate pathway for oxidative stress responses. Cell Cycle. 2:9–10; 2003.
Taylor, G.; Konstantinova, I.; Sonnenfeld, G.; Jennings, R. Changes in the immune system during and after space flight. Adv. Space Biol. Med. 6:1–32; 1997.
Taylor, J. M.; Crack, P. J. Impact of oxidative stress on neuronal survival. Clin. Exp. Pharm. & Phy. 31:397–406; 2004.
Wang, X.; Martindale, J. L.; Liu, Y.; Holbrook, N. J. The cellular response to oxidative stress: influences of mitogen activated protein kinase signaling pathways on cell survival. Biochem. J. 333:291–300; 1998.
Wu, G.; Fang, Y. Z.; Yang, S.; Lupton, J. R.; Turner, N. D. Glutathione metabolism and its implications for health. J. Nutr. 134: 489–492; 2004.
Yamamoto, Y.; Gaynor, R. Role of NF-kB pathway in the pathogenesis of human disease states. Curr. Mol. Med. 1:287–296; 2001.
Yamauchi, K.; Hales, N.; Robinson, S.; Neihoff, M.; Ramesh, V.; Pellis, N. R. Kulkarni, A. Dietary nucleotides prevent decrease in cellular immunity in ground-based microgravity analog. J. Appl. Physiol. 93:161–166; 2002.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Wise, K.C., Manna, S.K., Yamauchi, K. et al. Activation of nuclear transcription factor-κB in mouse brain induced by a simulated microgravity environment. In Vitro Cell.Dev.Biol.-Animal 41, 118–123 (2005). https://doi.org/10.1290/0501006.1
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1290/0501006.1