p38γ/δ activation alters cardiac electrical activity and predisposes to ventricular arrhythmia.
Animals
Mitogen-Activated Protein Kinase 12
/ metabolism
Ryanodine Receptor Calcium Release Channel
/ metabolism
Ventricular Fibrillation
/ physiopathology
Action Potentials
/ drug effects
Disease Models, Animal
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 13
/ metabolism
Phosphorylation
Myocytes, Cardiac
/ metabolism
Male
Enzyme Activation
Mice
Ventricular Premature Complexes
/ physiopathology
Sarcoplasmic Reticulum
/ metabolism
Mice, Knockout
Humans
Calcium Signaling
Age Factors
Journal
Nature cardiovascular research
ISSN: 2731-0590
Titre abrégé: Nat Cardiovasc Res
Pays: England
ID NLM: 9918284280206676
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
received:
11
01
2023
accepted:
19
10
2023
medline:
28
8
2024
pubmed:
28
8
2024
entrez:
28
8
2024
Statut:
ppublish
Résumé
Ventricular fibrillation (VF) is a leading immediate cause of sudden cardiac death. There is a strong association between aging and VF, although the mechanisms are unclear, limiting the availability of targeted therapeutic interventions. Here we found that the stress kinases p38γ and p38δ are activated in the ventricles of old mice and mice with genetic or drug-induced arrhythmogenic conditions. We discovered that, upon activation, p38γ and p38δ cooperatively increase the susceptibility to stress-induced VF. Mechanistically, our data indicate that activated p38γ and p38δ phosphorylate ryanodine receptor 2 (RyR2) disrupt Kv4.3 channel localization, promoting sarcoplasmic reticulum calcium leak, I
Identifiants
pubmed: 39196141
doi: 10.1038/s44161-023-00368-x
pii: 10.1038/s44161-023-00368-x
doi:
Substances chimiques
Mitogen-Activated Protein Kinase 12
EC 2.7.1.-
Ryanodine Receptor Calcium Release Channel
0
Mitogen-Activated Protein Kinase 13
EC 2.7.1.-
ryanodine receptor 2. mouse
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
1204-1220Subventions
Organisme : Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)
ID : PDC2021-121147-I00
Organisme : Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)
ID : PGC2018-097019-B-I00
Organisme : Ministry of Economy and Competitiveness | Agencia Estatal de Investigación (Spanish Agencia Estatal de Investigación)
ID : PID2022-138525OB-I00
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : PMP21/00057
Organisme : Ministry of Economy and Competitiveness | Instituto de Salud Carlos III (Institute of Health Carlos III)
ID : PDC2021-121147-I00
Organisme : Ministerio de Educación, Cultura y Deporte (Ministry of Education, Culture and Sports, Spain)
ID : FPU17/03847
Organisme : "la Caixa" Foundation (Caixa Foundation)
ID : HR17-00247
Organisme : "la Caixa" Foundation (Caixa Foundation)
ID : HR19/52160013
Organisme : American Heart Association (American Heart Association, Inc.)
ID : 14POST17820005
Organisme : American Heart Association (American Heart Association, Inc.)
ID : 18POST34080175
Organisme : U.S. Department of Health & Human Services | NIH | National Heart, Lung, and Blood Institute (NHLBI)
ID : R01 Grant HL122352
Informations de copyright
© 2023. The Author(s), under exclusive licence to Springer Nature Limited.
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