Redox Signaling and Its Impact on Skeletal and Vascular Responses to Spaceflight

Abstract

Spaceflight entails exposure to numerous environmental challenges with the potential to contribute to both musculoskeletal and vascular dysfunction. The purpose of this review is to describe current understanding of microgravity and radiation impacts on the mammalian skeleton and associated vasculature at the level of the whole organism. Recent experiments from spaceflight and ground-based models have provided fresh insights into how these environmental stresses influence mechanisms that are related to redox signaling, oxidative stress, and tissue dysfunction. Emerging mechanistic knowledge on cellular defenses to radiation and other environmental stressors, including microgravity, are useful for both screening and developing interventions against spaceflight-induced deficits in bone and vascular function.

Keywords: antioxidant; bone; hindlimb unloading; microgravity; oxidative stress; radiation; reactive oxygen species; spaceflight; vasculature.

Figure 1

Hypothetical model on how spaceflight leads to deficits in tissue function and structural integrity. Exposure of tissues to elements of the spaceflight environment such as microgravity and radiation (and potentially other unknown factors) leads to enhanced production of reactive oxygen species (ROS) and reactive nitrogen species (NOS), increased levels of pro-inflammatory signals, and downregulation of endogenous antioxidant defenses. This leads to excess ROS/NOS due to an imbalance between endogenous antioxidant protein levels and ROS/NOS production. Excess ROS/NOS leads to oxidative damage of proteins, lipids and DNA which in turn result in deficits in tissue function and structural integrity. Other non-redox signaling processes may also contribute to these deficits. Some exogenous antioxidants found in the diet may block the increases in ROS/NOS levels and inflammatory signals, thereby preventing oxidative damage. It remains to be elucidated whether inflammation causes ROS production and/or vice versa in the context of spaceflight, and whether oxidative damage mediates or results from progressive tissue degeneration as a consequence of spaceflight. T-bar arrow: inhibitory effect; dotted line arrow: cause and effect needs further elucidation. Gray arrows depict the contribution of non-redox related processes in spaceflight-induced deficits in tissue structure and function.