Simulated microgravity alters differentiation and increases apoptosis in human follicular thyroid carcinoma cells

Abstract

This study focuses on the effects of simulated microgravity (0g) on the human follicular thyroid carcinoma cell line ML-1. Cultured on a three-dimensional clinostat, ML-1 cells formed three-dimensional MCTSs (MCTS diameter: 0.3 +/- 0.01 mm). After 24 and 48 h of clinorotation, the cells significantly decreased fT3 and fT4 secretion but up-regulated the thyroid-stimulating hormone-receptor expression as well as the production of vimentin, vinculin, and extracellular matrix proteins (collagen I and III, laminin, fibronectin, chondroitin sulfate) compared with controls. Furthermore, ML-1 cells grown on the clinostat showed elevated amounts of the apoptosis-associated Fas protein, of p53, and of bax but showed reduced quantities of bcl-2. In addition, signs of apoptosis became detectable, as assessed by terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick end labeling, 4', 6-diamidino-2-phenylindole staining, DNA laddering, and 85-kDa apoptosis-related cleavage fragments. These fragments resulted from enhanced 116-kDa poly(ADP-ribose)polymerase (PARP) activity and apoptosis. These observations suggest that clinorotation elevates intermediate filaments, cell adhesion molecules, and extracellular matrix proteins and simultaneously induces apoptosis in follicular thyroid cancer cells. In conclusion, our experiments could provide a regulatory basis for the finding that astronauts show low thyroid hormone levels after space flight, which may be explained by the increase of apoptosis in thyrocytes as a result of simulated 0g.

Modeled gravitational unloading triggers differentiation and apoptosis in preosteoclastic cells

“…In fact, in FLG 29.1 cells exposed to the RPM, both Fas and FasL resulted overexpressed, compared to the controls, thus suggesting the triggering of the extrinsic pathway. In accordance with data reported by other authors [Grimm et al, 2002;Uva et al, 2002;Carlsson et al, 2003], we found cytoskeletal alterations as well. In particular, the cytoskeletal intermediate filament protein vimentin increased, while a-actin, F-actin, and tubulin decreased.…”

“…Moreover, the involvement of both the extrinsic and intrinsic pathways was demonstrated. In cells exposed to low g, enhanced expression of the death receptor Fas, activating the extrinsic pathway, was detected [Lewis et al, 1998;Grimm et al, 2002]. It was also found that hypogravity-induced apoptosis is accompanied by an alteration of the cytoskeleton, resulting in redistribution and then dissolution of the mitochondria [Schatten et al, 2001;Kossmehl et al, 2003], as occurs in the intrinsic mitochondrial-mediated cell death program [Shimizu et al, 2000].…”

“…Several authors reported an increase in apoptosis in different cell types cultured both in real and modeled hypogravity [Lewis et al, 1998;Schatten et al, 2001;Grimm et al, 2002]. Moreover, the involvement of both the extrinsic and intrinsic pathways was demonstrated.…”

Simulated hypogravity impairs the angiogenic response of endothelium by up-regulating apoptotic signals

“…The induction of apoptosis has been reported in different cell lines in simulated hypogravity [26,27]. It is established that cell exposure to both real and simulated hypogravity conditions causes cytoskeleton disorganization associated with microtubule disruption [28].…”

Simulation of Microgravity by Magnetic Levitation and Random Positioning: Effect on Human A431 Cell Morphology

“…The random rotation in all directions results in a net force of zero. Simulation of weightlessness with the RPM was reported to result in a wide variety of cellular responses which have also been found partly under real microgravity conditions (Hoson et al 1997;Schwarzenberg et al 1998;Grimm et al 2002;Uva et al 2002;Infanger et al 2006;Ulbrich et al 2008;Versari et al 2007a, b).…”