Transcriptomics, NF-κB Pathway, and Their Potential Spaceflight-Related Health Consequences

Abstract

In space, living organisms are exposed to multiple stress factors including microgravity and space radiation. For humans, these harmful environmental factors have been known to cause negative health impacts such as bone loss and immune dysfunction. Understanding the mechanisms by which spaceflight impacts human health at the molecular level is critical not only for accurately assessing the risks associated with spaceflight, but also for developing effective countermeasures. Over the years, a number of studies have been conducted under real or simulated space conditions. RNA and protein levels in cellular and animal models have been targeted in order to identify pathways affected by spaceflight. Of the many pathways responsive to the space environment, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) network appears to commonly be affected across many different cell types under the true or simulated spaceflight conditions. NF-κB is of particular interest, as it is associated with many of the spaceflight-related health consequences. This review intends to summarize the transcriptomics studies that identified NF-κB as a responsive pathway to ground-based simulated microgravity or the true spaceflight condition. These studies were carried out using either human cell or animal models. In addition, the review summarizes the studies that focused specifically on NF-κB pathway in specific cell types or organ tissues as related to the known spaceflight-related health risks including immune dysfunction, bone loss, muscle atrophy, central nerve system (CNS) dysfunction, and risks associated with space radiation. Whether the NF-κB pathway is activated or inhibited in space is dependent on the cell type, but the potential health impact appeared to be always negative. It is argued that more studies on NF-κB should be conducted to fully understand this particular pathway for the benefit of crew health in space.

Metabolic Pathways of the Warburg Effect in Health and Disease: Perspectives of Choice, Chain or Chance

“…The scope of relevance for the Warburg effect has extended well beyond its origins as an anomaly of cancer. It is clear that, for any long-term space mission, astronauts will need appropriate physical shielding and additional medicinal countermeasures to limit both excessive oxidative stress triggered by ionizing radiation and the associated inflammatory processes mediated by the NF-κB pathway [ 162 ]. Use of cytoprotective agents, such as Amifostine, can provide radioprotection to normal tissues by triggering a metabolic shift with induction of glycolysis and blockage of mitochondrial pyruvate usage through a Warburg effect pathway that reduces ROS production [ 163 ].…”

The Influence of Radiation on Bone and Bone Cells—Differential Effects on Osteoclasts and Osteoblasts

“…Therefore, a direct comparison between the low LET IR that is commonly used for medical applications and the high LET IR that astronauts are exposed to in space is not feasible, as high and low LET have different physical and biological properties [ 87 , 88 ]. Cosmic radiation has numerous negative effects on the human body during space travel, with the most prominent ones being a significant increase in the individual cancer risk, cardiovascular deconditioning, changes in the immune system and also alterations in bone homeostasis, and consequently in a loss of bone mass [ 89 , 90 ]. In addition, microgravity in space further promotes bone loss, making the space environment especially deleterious for the skeletal system and bone [ 91 ].…”

Oxidative Stress and Space Biology An Organ-Based Approach

“…It is clear that, for any long-term space mission, astronauts will need appropriate physical shielding and additional medicinal countermeasures to limit both excessive oxidative stress triggered by ionizing radiation and the associated inflammatory processes mediated by the NF-κB pathway [162]. Use of cytoprotective agents, such as Amifostine, can provide radioprotection to normal 129 …”