Biological and metabolic response in STS-135 space-flown mouse skin

Abstract

There is evidence that space flight condition-induced biological damage is associated with increased oxidative stress and extracellular matrix (ECM) remodeling. To explore possible mechanisms, changes in gene expression profiles implicated in oxidative stress and in ECM remodeling in mouse skin were examined after space flight. The metabolic effects of space flight in skin tissues were also characterized. Space Shuttle Atlantis (STS-135) was launched at the Kennedy Space Center on a 13-day mission. Female C57BL/6 mice were flown in the STS-135 using animal enclosure modules (AEMs). Within 3-5 h after landing, the mice were euthanized and skin samples were harvested for gene array analysis and metabolic biochemical assays. Many genes responsible for regulating production and metabolism of reactive oxygen species (ROS) were significantly (p < 0.05) altered in the flight group, with fold changes >1.5 compared to AEM control. For ECM profile, several genes encoding matrix and metalloproteinases involved in ECM remodeling were significantly up-/down-regulated following space flight. To characterize the metabolic effects of space flight, global biochemical profiles were evaluated. Of 332 named biochemicals, 19 differed significantly (p < 0.05) between space flight skin samples and AEM ground controls, with 12 up-regulated and 7 down-regulated including altered amino acid, carbohydrate metabolism, cell signaling, and transmethylation pathways. Collectively, the data demonstrated that space flight condition leads to a shift in biological and metabolic homeostasis as the consequence of increased regulation in cellular antioxidants, ROS production, and tissue remodeling. This indicates that astronauts may be at increased risk for pathophysiologic damage or carcinogenesis in cutaneous tissue.

Proteomic Analysis of Mouse Brain Subjected to Spaceflight

“…Consistent with our previous results in the liver and skin from these same mice where we found that spaceflight had a major impact on metabolism [33,[60][61][62], the next broad category involved to be impacted by spaceflight in the brain include glycolysis and metabolism.…”

Is spaceflight-induced immune dysfunction linked to systemic changes in metabolism?

“…In support of this is the trend for a spaceflight-induced up-regulation of adrenal levels of corticosterone, an indicator of increased hypothalamus-pituitary-adrenal (HPA) activity. Metabolomic analysis of both the liver (presented here) and skin [54] of these mice showed similar increases in corticosterone levels. This is also generally consistent with reports of post-flight increases in circulating corticosterone levels in rodent models [7, 17, 26, 55].…”

Simulated microgravity triggers epithelial mesenchymal transition in human keratinocytes

“…Consistent with this hypothesis, the expression profiles of many different genes of human keratinocytes are affected under exposure to simulated microgravity in a time-dependent manner and during recovery 14 . In addition, it has been recently reported that long term exposure to microgravity conditions is able to affect mouse skin homeostasis 15, 16 , mostly inducing expression modulations of those genes responsible for remodeling of the extracellular matrix 15 and leading to dermal atrophy 16 : however, the physiological behaviour of the epidermal keratinocytes and their molecular pattern did not appear significantly altered in such environment 16 . Therefore, in the present paper, we searched for changes on the regenerative ability and response to tissue damage of human epidermal cells through the analysis of the effects of the simulated microgravity on the repair process.…”