Simulated microgravity promotes cellular senescence via oxidant stress in rat PC12 cells

Wang, Jinghua; Zhang, Jifei; Bai, Shasha; Wang, Guangyou; Li-li, MU; Sun, Bo; Wang, Dandan; Kong, Qingfei; Liu, Yumei; Yao, Xiuhua; Xu, Ying; Li, Hulun

doi:10.1016/j.neuint.2009.07.002

Cited by 60 publications

(43 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Notably, these three genes are targets of the nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) which induces transcription of cytoprotective genes containing antioxidant response elements (19). The transcription factor Nrf2 may therefore play a cytoprotective role against a possible oxidative stress induced by the RPM, which is in line with previous observations of increased oxidative stress in simulated microgravity (20)(21)(22).…”

Section: The Rpm Has a Dominant Impact On Single Gene Expressionsupporting

confidence: 84%

Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts

Beck

Moreels

Quintens

et al. 2014

International Journal of Molecular Medicine

View full text Add to dashboard Cite

Abstract. microgravity and cosmic rays as found in space are difficult to recreate on earth. However, ground-based models exist to simulate space flight experiments. In the present study, an experimental model was utilized to monitor gene expression changes in fetal skin fibroblasts of murine origin. Cells were continuously subjected for 65 h to a low dose (55 mSv) of ionizing radiation (IR), comprising a mixture of high-linear energy transfer (LET) neutrons and low-LET gamma-rays, and/or simulated microgravity using the random positioning machine (RPM), after which microarrays were performed. The data were analyzed both by gene set enrichment analysis (GSEA) and single gene analysis (SGA). Simulated microgravity affected fetal murine fibroblasts by inducing oxidative stress responsive genes. Three of these genes are targets of the nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), which may play a role in the cell response to simulated microgravity. In addition, simulated gravity decreased the expression of genes involved in cytoskeleton remodeling, which may have been caused by the downregulation of the serum response factor (SRF), possibly through the Rho signaling pathway. Similarly, chronic exposure to low-dose IR caused the downregulation of genes involved in cytoskeleton remodeling, as well as in cell cycle regulation and DNA damage response pathways. Many of the genes or gene sets that were altered in the individual treatments (RPM or IR) were not altered in the combined treatment (RPM and IR), indicating a complex interaction between RPM and IR.

show abstract

Section: The Rpm Has a Dominant Impact On Single Gene Expressionsupporting

confidence: 84%

Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts

Beck

Moreels

Quintens

et al. 2014

International Journal of Molecular Medicine

View full text Add to dashboard Cite

show abstract

“…This oxidative stress response has been observed in various regions of the brain in rats subjected to 1-4 weeks of microgravity simulation by tail suspension [37]. Recently, Wang et al also reported that the activity of intracellular antioxidant enzymes was significantly increased at 12 h after the microgravity onset, yet decreased at 96 h, and stimulated microgravity promotes cellular senescence via oxidant stress in rat PC12 cells [11].…”

Section: Discussionmentioning

confidence: 70%

“…In vitro studies show that an abundance of NO is produced in PC12 and SH-SY5Y cells [9], while protein nitration is increased in PC12 cells [10]. Recent study showed that exposure to SMG induces cellular senescence in PC12 cells via an increased oxidative stress [11]. In particular, genes involved in oxidoreductase activity are the ones most significantly differentially expressed [12] under conditions of SMG produced either by a rotating wall bioreactor with a high aspect ratio vessel or by a clinostat.…”

Section: Introductionmentioning

confidence: 99%

Protective Effects of Flavonoids Against Oxidative Stress Induced by Simulated Microgravity in SH-SY5Y Cells

Chen

Liu

et al. 2010

Neurochem Res

View full text Add to dashboard Cite

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.

show abstract

“…Influences of microgravity on endothelial cell behavior have been suggested by a number of reports, describing alterations in proliferation, gene expression pattern, and functional behavior (Carlsson et al 2003;Morbidelli et al 2005;Wang et al 2009a). Some of the results obtained in vitro offer an explanation to altered clinical and biochemical parameters during manned orbital space flight.…”

Section: Discussionmentioning

confidence: 99%

Impact of simulated microgravity on microvascular endothelial cell apoptosis

et al. 2011

View full text Add to dashboard Cite

Cardiovascular deconditioning is known to occur in astronauts exposed to microgravity. Endothelial dysfunction at microcirculatory sites might contribute to cardiovascular deconditioning induced by weightlessness. Recent studies have reported changes in the morphology and gene expression of endothelial cells exposed to conditions of simulated microgravity. The present study was aimed at examining the effects of microgravity on the apoptosis of microvascular endothelial cells and the mechanism underlying these effects. We simulated a microgravity environment and found that microgravity induced microvascular endothelial cell apoptosis and that this effect was correlated with the downregulation of the PI3K/Akt pathway, increased expression of NF-κB, and depolymerization of F-actin. These findings may provide important insights into the origin of the adverse physiological changes occurring due to exposure to microgravity conditions.

show abstract

Simulated microgravity promotes cellular senescence via oxidant stress in rat PC12 cells

Cited by 60 publications

References 41 publications

Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts

Chronic exposure to simulated space conditions predominantly affects cytoskeleton remodeling and oxidative stress response in mouse fetal fibroblasts

Protective Effects of Flavonoids Against Oxidative Stress Induced by Simulated Microgravity in SH-SY5Y Cells

Impact of simulated microgravity on microvascular endothelial cell apoptosis

Contact Info

Product

Resources

About