Nuclear Phosphatidylcholine and Sphingomyelin Metabolism of Thyroid Cells Changes during Stratospheric Balloon Flight

Abstract

Nuclear sphingomyelin and phosphatidylcholine metabolism is involved in the response to ultraviolet radiation treatment in different ways related to the physiological state of cells. To evaluate the effects of low levels of radiation from the stratosphere on thyroid cells, proliferating and quiescent FRTL-5 cells were flown in a stratospheric balloon (BIRBA mission). After recovery, the activity of neutral sphingomyelinase, phosphatidylcholine-specific phospholipase C, sphingomyelin synthase, and reverse sphingomyelin synthase was assayed in purified nuclei and the nuclei-free fraction. In proliferating FRTL-5, space radiation stimulate nuclear neutral sphingomyelinase and reverse sphingomyelin synthase activity, whereas phosphatidylcholine-specific phospholipase C and sphingomyelin synthase were inhibited, thus inducing sphingomyelin degradation and phosphatidylcholine synthesis. This effect was lower in quiescent cells. The possible role of nuclear lipid metabolism in the thyroid damage induced by space radiations is discussed.

Spaceflight Induced Disorders: Potential Nutritional Countermeasures

“…Moreover, in the thyroid tissue it was evident an overexpression of enzymes for sphingomyelin metabolism such as sphingomyelinase and sphingomyelin-synthase and, of thyroid stimulating hormone receptor (Albi et al, 2012). It is relevant that these results were opposite to those obtained in hypergravity condition (Albi et al, 2014a) and different from changes induced by UV radiation exposure (Albi et al, 2009). Interestingly, a change in an elevated microbiome alpha diversity and an altered microbial community structure were reported in mice after a 37-day spaceflight onboard the ISS (LaPelusa et al, 2021).…”

“…It has been extensively demonstrated that microgravity impacts the proteome in humans with consequent changes in various biological processes such as angiogenesis, apoptosis, cell adhesion, migration, proliferation, stress response, and signal transduction (Strauch et al, 2019). In thyroid cells, microgravity changes the expression and localization of the specific protein Galectin-3 (Albi et al, 2014b) and also induces the overexpression of enzymes such as sphingomyelinase and sphingomyelin-synthase and of the thyroid stimulating hormone receptor (Albi et al, 2012), the opposite to what happens in hypergravity (Albi et al, 2014a) and different from changes induced by radiation exposure (Albi et al, 2009). In overall, significant protein remodeling is induced specifically by microgravity.…”

Radiation and Thyroid Cancer

“…In proliferating cells, low doses of stratospheric radiation did not induce cell death but only early modifications of nuclear SM and PC metabolism. In purified nuclei, SMase and RSM-synthase activities were increased, whereas PC-PLC and SM-synthase activities were inhibited, leading to an increase of the ceramide/DAG ratio [ 63 ]. These studies indicated that nuclear SM metabolism was involved in radiation-induced damage ( Table 1 ).…”

Nuclear Sphingolipid Metabolism

“…To date, enzymes involved in SM, ceramide, SPH, and glycosphingolipid metabolism have been identified in nuclear extracts isolated from different cell types (42-44, 46, 48, 106-108). SM was the first sphingolipid identified as a component of the nuclear matrix (109).…”

“…As discussed above, SM is the most abundant sphingolipid in the nucleus and the major phospholipid associated with chromatin (10), although it is enriched three times higher in the nuclear matrix (103). Studies have demonstrated that nuclear SM levels are dynamic and oscillate in response to different cellular states (43, 45, 50, 106, 112, 119). Additionally, distinct cellular cues differentially affect SM concentration in distinct subnuclear compartments (e.g., nuclear matrix versus chromatin) (103).…”