Document Detail


Weightlessness induced apoptosis in normal thyroid cells and papillary thyroid carcinoma cells via extrinsic and intrinsic pathways.
MedLine Citation:
PMID:  12933692     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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 by 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.
Authors:
Peter Kossmehl; Mehdi Shakibaei; Augusto Cogoli; Manfred Infanger; Francesco Curcio; Johann Schönberger; Christoph Eilles; Johann Bauer; Holger Pickenhahn; Gundula Schulze-Tanzil; Martin Paul; Daniela Grimm
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Endocrinology     Volume:  144     ISSN:  0013-7227     ISO Abbreviation:  Endocrinology     Publication Date:  2003 Sep 
Date Detail:
Created Date:  2003-08-22     Completed Date:  2003-09-16     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  4172-9     Citation Subset:  AIM; IM; S    
Affiliation:
Institute of Clinical Pharmacology and Toxicology, Benjamin Franklin Medical Center, Freie Universität Berlin, 14195 Berlin, Germany.
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD95 / metabolism
Apoptosis / physiology*
Blotting, Western
Carcinoma, Papillary*
Caspase 3
Caspases / metabolism
Collagen Type I / metabolism
Extracellular Matrix Proteins / metabolism
Fibronectins / metabolism
Humans
Laminin / metabolism
Mitochondria / metabolism
Osteopontin
Poly(ADP-ribose) Polymerases / metabolism
Rotation
Sialoglycoproteins / metabolism
Thyroid Gland / cytology*
Thyroid Neoplasms*
Tumor Cells, Cultured / cytology,  metabolism
Weightlessness*
Chemical
Reg. No./Substance:
0/Antigens, CD95; 0/Collagen Type I; 0/Extracellular Matrix Proteins; 0/Fibronectins; 0/Laminin; 0/SPP1 protein, human; 0/Sialoglycoproteins; 106441-73-0/Osteopontin; EC 2.4.2.30/Poly(ADP-ribose) Polymerases; EC 3.4.22.-/CASP3 protein, human; EC 3.4.22.-/Caspase 3; EC 3.4.22.-/Caspases

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