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Expression of hypoxia-inducible genes is suppressed in altered gravity due to impaired nuclear HIF1α accumulation.
Aboouf, Mostafa A; Thiel, Cora S; Borisov, Sergey M; Tauber, Svantje; Bönzli, Eva; Schetle, Nelli; Ullrich, Oliver; Gassmann, Max; Vogel, Johannes.
Afiliación
  • Aboouf MA; Vetsuisse Faculty, Institute of Veterinary Physiology, University of Zurich, Winterthurerstrasse 260, 8057, Zurich, Switzerland. mostafaaboouf.ali@uzh.ch.
  • Thiel CS; Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland. mostafaaboouf.ali@uzh.ch.
  • Borisov SM; Vetsuisse Faculty, Center for Clinical Studies, University of Zurich, 8057, Zurich, Switzerland. mostafaaboouf.ali@uzh.ch.
  • Tauber S; Department of Biochemistry, Faculty of Pharmacy, Ain Shams University, Cairo, 11566, Egypt. mostafaaboouf.ali@uzh.ch.
  • Bönzli E; Faculty of Medicine, Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
  • Schetle N; UZH Space Hub, Air Force Center, Air Base Dübendorf, Überlandstrasse 270, 8600, Dubendorf, Switzerland.
  • Ullrich O; Institute of Analytical Chemistry and Food Chemistry, Graz University of Technology, Stremayrgasse 9, 8010, Graz, Austria.
  • Gassmann M; Faculty of Medicine, Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, 8057, Zurich, Switzerland.
  • Vogel J; UZH Space Hub, Air Force Center, Air Base Dübendorf, Überlandstrasse 270, 8600, Dubendorf, Switzerland.
Sci Rep ; 13(1): 14514, 2023 09 04.
Article en En | MEDLINE | ID: mdl-37666879
Extravehicular activities, the backbone of manned space exploration programs, set astronauts into mild hypoxia. Unfortunately, microgravity aggravates threatening symptoms of hypoxia such as vision impairment and brain edema. Hypoxia-inducible factors (HIFs) sense cellular hypoxia and, subsequently, change the cells' expression profile instantaneously by rapidly translocating-most likely cytoskeleton-dependently-into the nucleus and subsequently forming transcription complexes with other proteins. We tested the hypothesis that this fundamental process could be altered by sudden changes in gravitational forces in parabolic flights using a newly developed pocket-size cell culture lab that deoxygenizes cells within 15 min. Sudden gravity changes (SGCs 1g-1.8g-0g-1.8g-1g) during hypoxic exposure suppressed expression of the HIF1α-dependent genes investigated as compared with hypoxia at constant 1g. Normoxic cells subjected to SGCs showed reduced nuclear but not cytoplasmatic HIF1α signal and appeared to have disturbed cytoskeleton architecture. Inhibition of the actin-dependent intracellular transport using a combination of myosin V and VI inhibitors during hypoxia mimicked the suppression of the HIF1α-dependent genes observed during hypoxic exposure during SGCs. Thus, SGCs seem to disrupt the cellular response to hypoxia by impairing the actin-dependent translocation of HIF1α into the nucleus.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Actinas / Gravedad Alterada / Hipoxia Límite: Humans Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Actinas / Gravedad Alterada / Hipoxia Límite: Humans Idioma: En Revista: Sci Rep Año: 2023 Tipo del documento: Article País de afiliación: Suiza Pais de publicación: Reino Unido