Intermittent Hypoxia-Induced Cardiomyocyte Death Is Mediated by HIF-1 Dependent MAM Disruption.
cardiomyocyte death
hypoxia inducible factor-1
intermittent hypoxia
mitochondria associated-ER membrane
sleep disordered breathing
Journal
Antioxidants (Basel, Switzerland)
ISSN: 2076-3921
Titre abrégé: Antioxidants (Basel)
Pays: Switzerland
ID NLM: 101668981
Informations de publication
Date de publication:
27 Jul 2022
27 Jul 2022
Historique:
received:
20
06
2022
revised:
19
07
2022
accepted:
20
07
2022
entrez:
26
8
2022
pubmed:
27
8
2022
medline:
27
8
2022
Statut:
epublish
Résumé
Intermittent hypoxia (IH) is one of the main features of sleep-disordered breathing (SDB). Recent findings indicate that hypoxia inducible factor-1 (HIF-1) promotes cardiomyocytes apoptosis during chronic IH, but the mechanisms involved remain to be elucidated. Here, we hypothesize that IH-induced ER stress is associated with mitochondria-associated ER membrane (MAM) alteration and mitochondrial dysfunction, through HIF-1 activation. Right atrial appendage biopsies from patients with and without SDB were used to determine HIF-1α, Grp78 and CHOP expressions. Wild-type and HIF-1α In human atrial biopsies and mice, IH induced HIF-1 activation, ER stress and apoptosis. IH disrupted MAM, altered Ca IH-induced ER stress, MAM alterations and mitochondrial dysfunction were mediated by HIF-1; all these intermediate mechanisms ultimately inducing cardiomyocyte apoptosis. This suggests that HIF-1 modulation might limit the deleterious cardiac effects of SDB.
Identifiants
pubmed: 36009181
pii: antiox11081462
doi: 10.3390/antiox11081462
pmc: PMC9405320
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : Agence Nationale de la Recherche
ID : ANR-15-IDEX-02
Organisme : Else-Kroener Fresenius Foundation
ID : 2018_A159
Organisme : Deutsche Forschungsgemeinschaft
ID : WA 2539/4-1, 5-1, 7-1, and 8-1
Organisme : DFG SFB 1350 grant
ID : 387509280, TPA6
Organisme : the ReForM C
ID : XXX
Organisme : Fondation de France
ID : XXX
Organisme : Agir Pour les Maladies Chroniques
ID : XXX
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