PXD060084 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Proteomic surveys of the mouse heart unveil cardiovascular responses to nitric oxide/cGMP signaling deficiencies. |
Description | Nitric oxide (NO) is an important signaling molecule in the cardiovascular system. Reduced bioavailability of NO results in debilitated signaling, which contributes to the pathogenesis of cardiometabolic disorders. However, the alterations in signaling under NO deficiency remain mostly unknown. To gain an appreciation of the signaling landscapes during NO deficiency we combined genetics and proteomics to quantify changes in the heart proteome, phosphoproteome, and S-nitrosocysteine proteome in mice lacking each of the nitric oxide synthases, NOS1, NOS2, and NOS3, mice lacking all three enzymes (tNOS), or the alpha 1-regulatory subunit of the soluble guanylate cyclase (sGCα1). Modest changes, less than 1% in the proteome and 4% in the phosphoproteome were quantified in single NOS gene or sGCα1 deletion mouse hearts indicating sufficient biological compensation. In contrast, the absence of a single NOS gene reduced the number of S-nitrosylated proteins by 80%, 57%, and 35% in NOS3, NOS1, and NOS2 null mice respectively. The profound deficit of S-nitrosylated proteins in the NOS3 null mice was localized in metabolic pathways, which may explain the metabolic dysregulation that develops in these mice. A 21% remodeling of the proteome and 9% of the phosphoproteome was quantified in the tNOS null mice. We quantified changes in the levels and regulation of integral kinases indicating an adaptive rewiring of signaling to secure essential functions such as contraction and metabolism in the tNOS null mice. The data revealed the emergence of enhanced mitogen-activated-kinases Mapk3/Mapk1 signaling documented by increased phosphorylation of these two kinases and their downstream targets in the sGCα1 and tNOS null mice. These data highlight that adaptive compensation of signaling prevents overt phenotypes during NO signaling deficits, whereas maladaptive signaling via Mapk3/Mapk1 may promote cardiac dysfunction and pathological cardiomyopathy that progressively develops in the tNOS null mice. |
HostingRepository | PRIDE |
AnnounceDate | 2025-04-29 |
AnnouncementXML | Submission_2025-04-29_10:21:42.868.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Hossein Fazelinia |
SpeciesList | scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; |
ModificationList | phosphorylated residue |
Instrument | Orbitrap Exploris 480 |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2025-01-22 13:19:57 | ID requested | |
⏵ 1 | 2025-04-29 10:21:43 | announced | |
Publication List
Dataset with its publication pending |
Keyword List
submitter keyword: Heart, cGMP Signaling, Cardiometabolic Disorders,Nitric oxide |
Contact List
Harry Ischiropoulos, PhD |
contact affiliation | Children's Hospital of Philadelphia, Department of Pediatrics, Division of Neonatology, 416B4 ARC, 3615 Civic Center Blvd, Philadelphia, PA, 19104-4318, USA |
contact email | ischirop@pennmedicine.upenn.edu |
lab head | |
Hossein Fazelinia |
contact affiliation | Children's Hospital of Philadelphia |
contact email | fazeliniah@email.chop.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
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[ - ]
- PRIDE
- PXD060084
- Label: PRIDE project
- Name: Proteomic surveys of the mouse heart unveil cardiovascular responses to nitric oxide/cGMP signaling deficiencies.