Abstract:Exposure to altered microgravity during space travel induces changes in the brain and these are reflected in many of the physical behavior seen in the astronauts. The vulnerability of the brain to microgravity stress has been reviewed and reported. Identifying microgravity-induced changes in the brain proteome may aid in understanding the impact of the microgravity environment on brain function. In our previous study we have reported changes in specific proteins under simulated microgravity in the hippocampus … Show more
“…Data are expressed as mean ± SEM (n = 8). * P \ 0.05, ** P \ 0.01 compared with the static control group Neurochem Res (2010) 35:1445-1454 1451 shows that the nervous system is especially vulnerable to oxidative stress during microgravity conditions [5][6][7][8]. With continuing advancements in aerospace technology and more prolonged space flights, two things will become increasingly important in order to ensure the safety of prolonged space travel: an increased understanding-at both the organismal and cellular levels-of the effects of microgravity on the nervous system, and the taking of some effective measurements to achieve this.…”
Section: Discussionmentioning
confidence: 99%
“…Lipid peroxidation products (malondialdehyde, MDA) are increased in rats that are tail-suspended for 2 or 3 weeks to simulate microgravity [5,6]. A previous study detected lowered glutathione, decreased superoxide dismutase 2 (SOD2), and increased malate dehydrogenase and peroxiredoxin-6 in the hypothalamus of mice exposed to SMG, reflecting a reduction of antioxidant system function [7]. In another study, ROS are increased-with a concomitant decrease in glutathione-in brain stem and frontal cortex of mice exposed for 7 days to SMG [8].…”
Many lines of evidence suggest that microgravity results in increased oxidative stress in the nervous system. In order to protect neuronal cells from oxidative damage induced by microgravity, we selected some flavonoids that might prevent oxidative stress because of their antioxidant activities. Among the 20 flavonoids we examined, we found that isorhamnetin and luteolin had the best protective effects against H(2)O(2) or SIN-1-induced cytotoxicity in SH-SY5Y cells. Using a clinostat to simulate microgravity, we found that isorhamnetin and luteolin treatment protected SH-SY5Y cells by preventing microgravity-induced increases in reactive oxygen species (ROS), nitric oxide (NO) and 3-nitrotyrosine (3-NT) levels, and a decrease in antioxidant power (AP). Moreover, isorhamnetin and luteolin treatment downregulated the expression of inducible nitric oxide synthase (iNOS), and oxidative stress was significantly inhibited by an iNOS inhibitor in SH-SY5Y cells exposed to simulated microgravity (SMG). These results indicate that isorhamnetin and luteolin could protect against microgravity-induced oxidative stress in neuroblastoma SH-SY5Y cells by inhibiting the ROS-NO pathway. These two flavonoids may have potential for preventing oxidative stress induced by space flight or microgravity.
“…Data are expressed as mean ± SEM (n = 8). * P \ 0.05, ** P \ 0.01 compared with the static control group Neurochem Res (2010) 35:1445-1454 1451 shows that the nervous system is especially vulnerable to oxidative stress during microgravity conditions [5][6][7][8]. With continuing advancements in aerospace technology and more prolonged space flights, two things will become increasingly important in order to ensure the safety of prolonged space travel: an increased understanding-at both the organismal and cellular levels-of the effects of microgravity on the nervous system, and the taking of some effective measurements to achieve this.…”
Section: Discussionmentioning
confidence: 99%
“…Lipid peroxidation products (malondialdehyde, MDA) are increased in rats that are tail-suspended for 2 or 3 weeks to simulate microgravity [5,6]. A previous study detected lowered glutathione, decreased superoxide dismutase 2 (SOD2), and increased malate dehydrogenase and peroxiredoxin-6 in the hypothalamus of mice exposed to SMG, reflecting a reduction of antioxidant system function [7]. In another study, ROS are increased-with a concomitant decrease in glutathione-in brain stem and frontal cortex of mice exposed for 7 days to SMG [8].…”
Many lines of evidence suggest that microgravity results in increased oxidative stress in the nervous system. In order to protect neuronal cells from oxidative damage induced by microgravity, we selected some flavonoids that might prevent oxidative stress because of their antioxidant activities. Among the 20 flavonoids we examined, we found that isorhamnetin and luteolin had the best protective effects against H(2)O(2) or SIN-1-induced cytotoxicity in SH-SY5Y cells. Using a clinostat to simulate microgravity, we found that isorhamnetin and luteolin treatment protected SH-SY5Y cells by preventing microgravity-induced increases in reactive oxygen species (ROS), nitric oxide (NO) and 3-nitrotyrosine (3-NT) levels, and a decrease in antioxidant power (AP). Moreover, isorhamnetin and luteolin treatment downregulated the expression of inducible nitric oxide synthase (iNOS), and oxidative stress was significantly inhibited by an iNOS inhibitor in SH-SY5Y cells exposed to simulated microgravity (SMG). These results indicate that isorhamnetin and luteolin could protect against microgravity-induced oxidative stress in neuroblastoma SH-SY5Y cells by inhibiting the ROS-NO pathway. These two flavonoids may have potential for preventing oxidative stress induced by space flight or microgravity.
“…More recently, a proteomic analysis of hippocampus of HU mice revealed changes in structural proteins coupled with the loss of proteins involved in cell metabolism (Sarkar et al 2006). Furthermore, a similar analysis performed in hypothalamus revealed alteration of biomarkers of oxidative stress indicating vulnerability of the hypothalamus to the stress generated by microgravity (Sarkar et al 2008). …”
Changes in gravitational force such as that experienced by astronauts during space flight induce a redistribution of fluids from the caudad to the cephalad portion of the body together with an elimination of normal head-to-foot hydrostatic pressure gradients. To assess brain gene profile changes associated with microgravity and fluid shift, a large-scale analysis of mRNA expression levels was performed in the brains of 2-week control and hindlimb-unloaded (HU) mice using cDNA microarrays. Although to different extents, all functional categories displayed significantly regulated genes indicating that considerable transcriptomic alterations are induced by HU. Interestingly, the TIC class (transport of small molecules and ions into the cells) had the highest percentage of upregulated genes, while the most down-regulated genes were those of the JAE class (cell junction, adhesion, extracellular matrix). TIC genes comprised 16% of those whose expression was altered, including sodium channel, nonvoltage-gated 1 beta (Scnn1b), glutamate receptor (Grin1), voltagedependent anion channel 1 (Vdac1), calcium channel beta 3 subunit (Cacnb3) and others. The analysis performed by Gene-MAPP revealed several altered protein classes and functional pathways such as blood coagulation and immune response, learning and memory, ion channels and cell junction. In particular, data indicate that HU causes an alteration in hemostasis which resolves in a shift toward a more hyper-coagulative state with an increased risk of venous thrombosis. Furthermore, HU treatment seems to impact on key steps of synaptic plasticity and learning processes.
“…Previous cDNA microarray experiments showed that ten genes in human T lymphocytes were upregulated and 79 downregulated under simulated microgravity (Lewis et al 2001). Besides, GST and superoxide dismutase-2 decreased in the mouse hypothalamus under simulated microgravity through two-dimensional gel and matrix-assisted laser desorption ionization time of flight analysis (Sarkar et al 2008).The results obtained here indicate that microgravity cannot always elevate the amount of the recombinant protein expression under any circumstance, which was at least related with the target protein and temperature. However, the underlying mechanism still needs to be further investigated in the future study.…”
Simulated microgravity has been reported to affect the gene, protein expression, and its function in the cells. Semicarbazide-sensitive amine oxidase (SSAO; E.C.1.4.3.6.) is widely distributed in vascular cells, smooth muscle cells, and adipocytes. It is noteworthy whether the expression of SSAO is affected under simulated microgravity or not. In this study, an SSAO-transformed Escherichia coli BL21 was constructed firstly. Then, a sensitive, selective, and accurate method based on high-performance liquid chromatography electrospray ionization triple quadrupole (HPLC-ESI-QQQ) was developed to determine the amount of SSAO in the E. coli BL21. The limit of detection and limit of quantification were 5.0 and 10 fmol, respectively. Finally, SSAO expression in the recombinant E. coli BL21 was evaluated with various gravity and temperature conditions by HPLC-ESI-QQQ analysis. It is interesting that the tendency in the alteration of SSAO under simulated microgravity showed temperature difference. At 18 °C, the amount of SSAO in the inclusion bodies and soluble fractions under the simulated microgravity increased by 83% and 116%, respectively, compared with normal gravity. However, the decrease by 38% and 49% in the inclusion bodies and soluble fractions under the simulated microgravity was observed at 37 °C. Results obtained here indicate that the SSAO expression under simulated microgravity is dramatically sensitive to the temperature. On the other hand, a novel bioreactor from this study may also be useful for the recombinant protein expression in the field of gene engineering.
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