PXD061556

PXD061556 is an original dataset announced via ProteomeXchange.

Title	Regulatory mechanism of BDH1 expression in sepsis-induced cardiomyopathy involving 2-hydroxyisobutyrylation antagonizing ubiquitination.
Description	Lysine 2-hydroxyisobutyrylation (Khib) is a novel post-translational modification (PTM) that regulates many biological processes; however, little is known about its role in sepsis-induced cardiomyopathy (SCM). Here, we report for the first time non-histone 2-hydroxyisobutyrylome in SCM rats. A significant decrease in lysine 2-hydroxyisobutyrylation (Khib) at the K74 site of the ketone body metabolizing enzyme 3-hydroxybutyrate dehydrogenase 1 (BDH1) was identified in the septic heart. Interestingly, both mRNA and protein levels of BDH1 were significantly increased in the septic heart. BDH1 deficiency exacerbated sepsis-induced myocardial dysfunction and altered metabolic pathways. Mechanistically, BDH1 was regulated transcriptionally and post-translationally under septic conditions. LPS promoted activating transcription factor 3 (ATF3)-mediated transcriptional activation of BDH1 and enhanced binding of (histone deacetylase 2) HDAC2 and (cullin 1) CUL1 to BDH1, leading to increased de-Khib and ubiquitination at the K74 site, which facilitated proteasomal degradation of BDH1. Ultimately, BDH1 was increased, which may be a response to the demand for energy rearrangement in SCM. Collectively, these results shed light on the importance of different forms of PTM crosstalk in the regulation of key energy metabolism enzymes under septic conditions.
HostingRepository	iProX
AnnounceDate	2025-03-06
AnnouncementXML	Submission_2025-03-06_19:13:39.666.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Tiening Zhang
SpeciesList	scientific name: Rattus norvegicus; NCBI TaxID: 10116;
ModificationList	2-hydroxyglycine observational artifact
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-03-06 19:13:20	ID requested
⏵ 1	2025-03-06 19:13:40	announced

Dataset with its publication pending

submitter keyword: ketone body, BDH1, sepsis, myocardial dysfunction, 2-hydroxyisobutyrylation

Tiening Zhang
contact affiliation	Shengjing Hospital of China Medical University
contact email	cmuztn@vip.qq.com
lab head
Tiening Zhang
contact affiliation	Shengjing Hospital of China Medical University
contact email	cmuztn@vip.qq.com
dataset submitter

iProX dataset URI