Thyroid Cell Growth: Sphingomyelin Metabolism as Non-Invasive Marker for Cell Damage Acquired during Spaceflight

Abstract

Prolonged spaceflights are known to elicit changes in human cardiovascular, musculoskeletal, and nervous systems, whose functions are regulated by the thyroid gland. It is known that sphingomyelin metabolism is involved in apoptosis (programmed cell death) of thyroid cells induced by UVC radiation, but at present no data exists with regard to this phenomenon, which occurs during space missions. The aim of this study was to analyze, for the first time, the effect of spaceflight on the enzymes of sphingomyelin metabolism, sphingomyelinase, and sphingomyelin synthase, and to determine whether the ratio between the two enzymes might be used as a possible marker for thyroid activity during space missions. Both quiescent thyroid cells and thyroid cells stimulated to proliferate with thyrotropin (TSH) were cultured during the Eneide and Esperia missions on the International Space Station. The results show that during space missions the cells treated with TSH grew only 1.5 ± 0.65-fold and, thus, behave similarly to quiescent cells, while on the ground the same cells, maintained in experimental conditions that reproduced those of the flight, grew 7.71 ± 0.67-fold. Comparison of the sphingomyelinase/sphingomyelin-synthase ratio and the levels of Bax, STAT3, and RNA polymerase II in proliferating, quiescent, pro-apoptotic, or apoptotic cells demonstrated that thyroid cells during space missions were induced into a pro-apoptotic state. Given its specificity and the small amount of cells needed for analysis, we propose the use of the sphingomyelinase/sphingomyelin-synthase ratio as a marker of functional status of thyroid cells during space missions. Further studies could lead to its use in real time during prolonged spaceflights.

Critical Role for the Protons in FRTL-5 Thyroid Cells: Nuclear Sphingomyelinase Induced-Damage

“…The spaceflight impaired cell growth of FRTL-5 exposed to TSH; thus, the cells became similar to quiescent cells with similar SMase and SM-synthase activities. More precisely the space environment induced the cells into a pro-apoptotic state, similar to that obtained with both TSH starvation and serum withdrawal [9]. Comparing the results in different experimental models [6,9], we demonstrated that the SMase/SM-synthase ratio changed in various functional states of the cells since its value was very high in apoptotic cells, medium in pro-apoptotic cells, low in proliferating cells and very low in quiescent cells.…”

“…Comparing the results in different experimental models [6,9], we demonstrated that the SMase/SM-synthase ratio changed in various functional states of the cells since its value was very high in apoptotic cells, medium in pro-apoptotic cells, low in proliferating cells and very low in quiescent cells. This parameter has been suggested to be a specific marker for cell function [9]. In fact, its value is low in quiescent cells and gradually increases in proliferating, pro-apoptotic and apoptotic cells [9].…”

“…In the stratosphere, depletion of ozone resulted in an enrichment of UV radiation content and global warming. It is interesting to notice that in a space environment the FRTL-5 cell changes occurred according to their physiological state, the effect being stronger in proliferating than in quiescent cells [9]. Cells did not present signs of DNA fragmentation characteristic of apoptotic process but, in contrast, showed strongly altered lipid metabolism with activation of nuclear N -SMase and inhibition of PC-PLC and SM-synthase [8].…”

Growing Tissues in Real and Simulated Microgravity: New Methods for Tissue Engineering

“…Based on the ratio of sphingomyelinase and sphingomyelin synthase, two enzymes responsible for the sphingomyelin metabolism, Albi et al were able to determine the state of rat thyroid cells (FRTL-5) returning from r-mg as proapoptotic. 120 Similar changes of the sphingomyelin metabolism could be detected in a single mouse returning after 91 days to Earth. Further, it could be shown that beside the activity of the proteins their location in the thyroid cells was altered.…”

“…[117][118][119] Since the beginning of the new millennium, three Space missions were carried out that either analyzed thyroid rat cells 120 or thyroids of mice 121 flown in Space. Based on the ratio of sphingomyelinase and sphingomyelin synthase, two enzymes responsible for the sphingomyelin metabolism, Albi et al were able to determine the state of rat thyroid cells (FRTL-5) returning from r-mg as proapoptotic.…”