PXD045996 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | p38γ/δ activation alters cardiac electrical activity and predisposes to ventricular arrhythmia |
Description | 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 find that the stress kinases p38 and p38/are activated in the ventricles of old mice and mice with genetic or drug-induced arrhythmogenic conditions. We discovered that upon activation, the increased activity of p38 and p38/ was cooperatively associated increase the with susceptibility to stress-induced VF. Mechanistically, our data indicate that activated p38 and p38wphosphorylatee identified ryanodine receptor 2 (RyR2) and disrupt Kv4.3 channel localization, as a new substrate of p38/. Our data indicate that phosphorylation of SAP97 by activated p38/ also disrupts Kv4.3 localization at the plasma membrane, promoting sarcoplasmic reticulum calcium leak, Ito current reduction and action potential duration prolongation. In turn, this led to aberrant intracellular calcium handling, premature ventricular complexes, and enhanced susceptibility to VF. The importance of this finding is evidenced by the fact that bBlocking this pathway protected genetically modified animals from VF development and reduced the VF duration in aged animals. We have identified p38/-driven phosphorylation of RyR2 and SAP97 as a novel trigger of VF. These results indicate that p38 and p38/ are a new potential therapeutic target for sustained VF prevention. |
HostingRepository | PRIDE |
AnnounceDate | 2024-10-22 |
AnnouncementXML | Submission_2024-10-22_06:06:17.205.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Juan A Lopez |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | phosphorylated residue; iodoacetamide derivatized residue |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2023-10-09 07:02:32 | ID requested | |
1 | 2023-10-18 08:47:41 | announced | |
⏵ 2 | 2024-10-22 06:06:17 | announced | 2024-10-22: Updated project metadata. |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Phosphoproteome |
isobaric labelling |
TMT |
Contact List
Juan A Lopez |
contact affiliation | Head, Proteomics Unit, CNIC |
contact email | jalopez@cnic.es |
lab head | |
Juan A Lopez |
contact affiliation | CNIC |
contact email | jalopez@cnic.es |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/10/PXD045996 |
PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD045996
- Label: PRIDE project
- Name: p38γ/δ activation alters cardiac electrical activity and predisposes to ventricular arrhythmia