Influence of Microgravity on Apoptosis in Cells, Tissues, and Other Systems In Vivo and In Vitro

Abstract

All life forms have evolved under the constant force of gravity on Earth and developed ways to counterbalance acceleration load. In space, shear forces, buoyance-driven convection, and hydrostatic pressure are nullified or strongly reduced. When subjected to microgravity in space, the equilibrium between cell architecture and the external force is disturbed, resulting in changes at the cellular and sub-cellular levels (e.g., cytoskeleton, signal transduction, membrane permeability, etc.). Cosmic radiation also poses great health risks to astronauts because it has high linear energy transfer values that evoke complex DNA and other cellular damage. Space environmental conditions have been shown to influence apoptosis in various cell types. Apoptosis has important functions in morphogenesis, organ development, and wound healing. This review provides an overview of microgravity research platforms and apoptosis. The sections summarize the current knowledge of the impact of microgravity and cosmic radiation on cells with respect to apoptosis. Apoptosis-related microgravity experiments conducted with different mammalian model systems are presented. Recent findings in cells of the immune system, cardiovascular system, brain, eyes, cartilage, bone, gastrointestinal tract, liver, and pancreas, as well as cancer cells investigated under real and simulated microgravity conditions, are discussed. This comprehensive review indicates the potential of the space environment in biomedical research.

Spaceflight Modulates the Expression of Key Oxidative Stress and Cell Cycle Related Genes in Heart

“…However, we cannot rule out the possibility that spaceflight activates DNA damage and apoptosis pathways in a smaller sub-population of cell types within the heart during spaceflight, as shown previously for exposure to low dose, heavy ion radiation ( 16 O, 600 MeV/n) simulating space radiation [61]. Evidence supporting the possibility that spaceflight activates DNA damage pathways and/or apoptosis has been reported for tissues other than heart [62], including the thymus [63,64] and the eye [62,64], and multiomics analyses reveal increased levels of DNA damage markers in urine and blood from astronauts [26].…”

Role of Apoptosis in Wound Healing and Apoptosis Alterations in Microgravity

“…There is evidence that exposure of lymphocytes to spaceflight as well as to simulated altered gravity conditions created by microgravity-simulating devices results in elevated apoptosis of immune cells (Prasad et al, 2020a). Lymphocytes cultured in simulated microgravity conditions exhibited elevated apoptosis and reduced cell proliferation (Girardi et al, 2014).…”

“…In addition to the effects of the change in mechanical forces in microgravity, space radiation is another influencing factor. DNA damage due to ionizing radiation leads to increased DNA repair, cell cycle arrest and apoptosis in various cell types (Prasad et al, 2020a).…”

Effect of Space Flight on the Behavior of Human Retinal Pigment Epithelial ARPE-19 Cells and Evaluation of Coenzyme Q10 Treatment

“…Cytoskeletal disorganization and significant changes in the expression of its main components, actin, tubulin and vimentin, both at phenotypic and genotypic levels have been observed in various cell type subjected to altered gravity conditions [40][41][42][43] and the complete destruction of the microtubule network was observed in Jurkat cells following exposure to real microgravity [44]. Similarly, in endothelial cells, a significant reduction in actin fibers was observed in response to simulated microgravity [45] and a significant increase in stress fibers following hypergravity [46].…”