Expression of hypoxia-inducible genes is suppressed in altered gravity due to impaired nuclear HIF1α accumulation.
Journal
Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288
Informations de publication
Date de publication:
04 09 2023
04 09 2023
Historique:
received:
12
04
2023
accepted:
30
08
2023
medline:
6
9
2023
pubmed:
5
9
2023
entrez:
4
9
2023
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 37666879
doi: 10.1038/s41598-023-41686-1
pii: 10.1038/s41598-023-41686-1
pmc: PMC10477221
doi:
Substances chimiques
Actins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
14514Informations de copyright
© 2023. Springer Nature Limited.
Références
J Cell Biol. 2019 May 6;218(5):1619-1633
pubmed: 30814157
Proc Natl Acad Sci U S A. 2016 Mar 1;113(9):E1162-9
pubmed: 26811464
Cancer Res. 2001 Oct 15;61(20):7388-93
pubmed: 11606367
FEBS Lett. 2012 Sep 21;586(19):3208-14
pubmed: 22884421
Cell Mol Biol Lett. 2022 Dec 8;27(1):109
pubmed: 36482296
Anal Chem. 2012 Aug 7;84(15):6723-30
pubmed: 22738322
J Exp Clin Cancer Res. 2010 Jan 14;29:2
pubmed: 20074327
Sci Rep. 2019 Aug 2;9(1):11276
pubmed: 31375732
Adv Wound Care (New Rochelle). 2014 May 1;3(5):390-399
pubmed: 24804159
Eur J Clin Invest. 2009 Aug;39(8):723-8
pubmed: 19473213
J Biol Chem. 1993 May 5;268(13):9604-10
pubmed: 8486648
Ann Emerg Med. 1987 Sep;16(9):974-9
pubmed: 3307557
Nat Struct Mol Biol. 2005 Feb;12(2):127-32
pubmed: 15665867
Aviat Space Environ Med. 2012 Oct;83(10):975-84
pubmed: 23066620
J Am Soc Nephrol. 2006 Mar;17(3):805-12
pubmed: 16421224
Prog Cardiovasc Dis. 2010 May-Jun;52(6):467-84
pubmed: 20417340
Biomolecules. 2022 Jul 01;12(7):
pubmed: 35883482
J Biol Chem. 1986 Dec 5;261(34):16033-6
pubmed: 3782106
J Clin Invest. 1989 Nov;84(5):1470-8
pubmed: 2478587
J Strength Cond Res. 2013 Sep;27(9):2420-6
pubmed: 23254545
Cell Death Differ. 2019 Sep;26(9):1716-1734
pubmed: 30464225
Cell Physiol Biochem. 2004;14(4-6):351-60
pubmed: 15319539
Am J Physiol Regul Integr Comp Physiol. 2004 Jun;286(6):R1063-8
pubmed: 14764437
Anal Chem. 2008 Dec 15;80(24):9435-42
pubmed: 19006407
Mol Cell Biol. 1996 Oct;16(10):5221-31
pubmed: 8816435
J Biol Chem. 2012 Apr 6;287(15):11859-69
pubmed: 22367210
Int J Mol Sci. 2021 Aug 30;22(17):
pubmed: 34502336
Brain Res. 2011 Mar 24;1381:1-10
pubmed: 20977891
FASEB J. 2001 May;15(7):1312-4
pubmed: 11344124
J Biol Chem. 2007 Aug 10;282(32):23316-25
pubmed: 17562702
J Biol Chem. 1995 Jan 20;270(3):1230-7
pubmed: 7836384
Sci Signal. 2009 Aug 11;2(83):pe49
pubmed: 19671926
Physiol Behav. 2019 Sep 1;208:112559
pubmed: 31128128
Biochem Soc Trans. 2003 Dec;31(Pt 6):1171-7
pubmed: 14641020
Cancer Res. 2005 Dec 1;65(23):11094-100
pubmed: 16322259
Blood. 2020 Mar 26;135(13):1066-1069
pubmed: 32043119
Nano Lett. 2011 Oct 12;11(10):4074-8
pubmed: 21882883
Cell. 2007 Nov 30;131(5):952-65
pubmed: 18045537
Cancer Res. 2005 Oct 1;65(19):9021-8
pubmed: 16204076
J Leukoc Biol. 2009 Nov;86(5):1017-8
pubmed: 19875627
Int J Mol Sci. 2021 Aug 06;22(16):
pubmed: 34445156
Cell Mol Life Sci. 2008 May;65(9):1378-89
pubmed: 18239852
High Alt Med Biol. 2015 Jun;16(2):125-37
pubmed: 26070057
Angew Chem Int Ed Engl. 2010 Nov 2;49(45):8484-8
pubmed: 20878825
J Biol Chem. 2004 Oct 22;279(43):44976-86
pubmed: 15322093
Curr Top Microbiol Immunol. 2010;345:105-20
pubmed: 20517715
J Cell Physiol. 1992 Jul;152(1):215-21
pubmed: 1618920
J Appl Physiol (1985). 1993 Mar;74(3):1100-6
pubmed: 8387070
J Cell Physiol. 2003 Jan;194(1):30-44
pubmed: 12447987
Int J Mol Med. 2020 Feb;45(2):385-400
pubmed: 31894249
Proc Natl Acad Sci U S A. 1986 Nov;83(21):8054-8
pubmed: 3534880
Int J Mol Sci. 2019 Jan 20;20(2):
pubmed: 30669540
Nat Cell Biol. 2005 Sep;7(9):861-9
pubmed: 16100513
Nature. 1992 Oct 29;359(6398):843-5
pubmed: 1279431
Hum Immunol. 2011 Jul;72(7):547-52
pubmed: 21513753
Curr Biol. 2007 Jun 19;17(12):R478-86
pubmed: 17580082
Am J Pathol. 2006 Nov;169(5):1843-54
pubmed: 17071605
FEBS Lett. 1999 Oct 29;460(2):251-6
pubmed: 10544245
Proc Natl Acad Sci U S A. 2020 Jul 7;117(27):15632-15641
pubmed: 32571914
Protein Sci. 2004 Oct;13(10):2825-8
pubmed: 15388866