PXD060084

PXD060084 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2025-01-22 13:19:57	ID requested
⏵ 1	2025-04-29 10:21:43	announced

Dataset with its publication pending

submitter keyword: Heart, cGMP Signaling, Cardiometabolic Disorders,Nitric oxide

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

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/2025/04/PXD060084

PRIDE project URI

• PRIDE
  1. PXD060084
     1. Label: PRIDE project
     2. Name: Proteomic surveys of the mouse heart unveil cardiovascular responses to nitric oxide/cGMP signaling deficiencies.