Weightlessness induced apoptosis in normal thyroid cells and papillary thyroid carcinoma cells via extrinsic and intrinsic pathways

Kossmehl, P. and Shakibaei, M. and Cogoli, A. and Infanger, M. and Curcio, F. and Schoenberger, Johann and Eilles, Christoph and Bauer, J. and Pickenhahn, H. and Schulze-Tanzil, G. and Paul, M. and Grimm, Daniela (2003) Weightlessness induced apoptosis in normal thyroid cells and papillary thyroid carcinoma cells via extrinsic and intrinsic pathways. ENDOCRINOLOGY, 144 (9). pp. 4172-4179. ISSN 0013-7227

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Abstract

Apoptosis plays a pivotal role in development, tissue homeostasis, cancer, immune defense, and response to weightlessness. It can be initiated by external signals via death receptors, but may also emerge from mitochondria. We exposed mitochondria-rich thyroid carcinoma cells (ONCO-DG1 cell line) and normal thyroid cells (HTU-5) to conditions of simulated microgravity. After 24 h, 10% of the cancer cells had entered a Fas-dependent apoptotic pathway, but destruction and redistribution of mitochondria, microtubuli disruption, and caspase-3 activation were also detected, demonstrating the activation of extrinsic as well as intrinsic pathways. Furthermore, ONCO-DG1 cells grown on the clinostat showed elevated amounts of Bax, but reduced quantities of bcl-2. In addition, signs of apoptosis became detectable, as assessed terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick end labeling, 4',6-diamidino-2-phenylindole staining, and 85-kDa apoptosis-related cleavage fragments. These fragments resulted from enhanced 116-kDa poly(ADP-ribose) polymerase activity and apoptosis. Apoptosis was also detected in normal HTU-5 cells, as demonstrated by electron microscopy, activation of caspase-3, increases in Fas and Bax, and elevation of 85-kDa apoptosis-related cleavage fragments resulting from enhanced poly(ADP-ribose) polymerase activity. Gravitational unloading affects the mitochondria and thereby may trigger apoptosis in thyroid cells subjected to weightlessness by clinorotation.

Item Type: Article
Uncontrolled Keywords: SIMULATED MICROGRAVITY; EXTRACELLULAR-MATRIX; FOLLICULAR CELLS; TUMOR-CELL; IN-VITRO; EXPRESSION; GRAVITY; RAT; SPACEFLIGHT; CLINOSTAT;
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Abteilung für Nuklearmedizin
Depositing User: Dr. Gernot Deinzer
Date Deposited: 30 Aug 2021 09:39
Last Modified: 30 Aug 2021 09:39
URI: https://pred.uni-regensburg.de/id/eprint/38649

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