Hypoxia-Induced Sarcoplasmic Reticulum Ca2+ Leak Is Reversed by Ryanodine Receptor Stabilizer JTV-519 in HL-1 Cardiomyocytes.
Journal
Anatolian journal of cardiology
ISSN: 2149-2271
Titre abrégé: Anatol J Cardiol
Pays: Turkey
ID NLM: 101652981
Informations de publication
Date de publication:
06 2022
06 2022
Historique:
entrez:
15
6
2022
pubmed:
16
6
2022
medline:
18
6
2022
Statut:
ppublish
Résumé
To assess whether hypoxia, as can be found in obstructive sleep apnea syndrome, is causally associated with the development of heart failure through a direct effect on calcium leakage from the sarcoplasmic reticulum. The impact of hypoxia on sarcoplasmic reticulum calcium leakage and expres- sion of RyR2 (ryanodine receptor2) and SERC2a (sarcoplasmic reticulum Ca2+ATPase 2a) was investigated together with the outcomes of JTV-519 and S107 treatment. HL-1 car- diomyocytes were cultured for 7 days on gas-permeable cultureware under control (12% O2) or hypoxic (1% O2) conditions with or without JTV-519 or S107. SRCL was assessed using a Fluo-5N probe. Gene and protein expression was analyzed using qPCR and western blotting. Hypoxic exposure increased sarcoplasmic reticulum calcium leakage by 39% and reduced RyR2 gene expression by 52%. No effect on RyR2 protein expression was observed. Treatment with 1μM JTV-519 reduced sarcoplasmic reticulum calcium leakage by 52% and 35% under control and hypoxic conditions, respectively. Administration of 1 μM JTV-519 increased RyR2 gene expression by 89% in control conditions. No effect on SRCL, RyR2, or SERC2a gene, or protein expression was observed with S107 treatment. Hypoxia increased sarcoplasmic reticulum calcium leakage which was ame- liorated by JTV-519 treatment independently of gene or protein expression. JTV-519 rep- resents a possible treatment for obstructive sleep apnea-associated HF.
Sections du résumé
BACKGROUND
To assess whether hypoxia, as can be found in obstructive sleep apnea syndrome, is causally associated with the development of heart failure through a direct effect on calcium leakage from the sarcoplasmic reticulum.
METHODS
The impact of hypoxia on sarcoplasmic reticulum calcium leakage and expres- sion of RyR2 (ryanodine receptor2) and SERC2a (sarcoplasmic reticulum Ca2+ATPase 2a) was investigated together with the outcomes of JTV-519 and S107 treatment. HL-1 car- diomyocytes were cultured for 7 days on gas-permeable cultureware under control (12% O2) or hypoxic (1% O2) conditions with or without JTV-519 or S107. SRCL was assessed using a Fluo-5N probe. Gene and protein expression was analyzed using qPCR and western blotting.
RESULTS
Hypoxic exposure increased sarcoplasmic reticulum calcium leakage by 39% and reduced RyR2 gene expression by 52%. No effect on RyR2 protein expression was observed. Treatment with 1μM JTV-519 reduced sarcoplasmic reticulum calcium leakage by 52% and 35% under control and hypoxic conditions, respectively. Administration of 1 μM JTV-519 increased RyR2 gene expression by 89% in control conditions. No effect on SRCL, RyR2, or SERC2a gene, or protein expression was observed with S107 treatment.
CONCLUSION
Hypoxia increased sarcoplasmic reticulum calcium leakage which was ame- liorated by JTV-519 treatment independently of gene or protein expression. JTV-519 rep- resents a possible treatment for obstructive sleep apnea-associated HF.
Identifiants
pubmed: 35703484
doi: 10.5152/AnatolJCardiol.2022.1223
pmc: PMC9361329
doi:
Substances chimiques
Ryanodine Receptor Calcium Release Channel
0
Thiazepines
0
K201 compound
0I621Y6R4Q
Calcium
SY7Q814VUP
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
476-484Références
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