PXD042103

PXD042103 is an original dataset announced via ProteomeXchange.

Title	HDL functionality is dependent on hepatocyte stress defense factors NRF1 and NRF2
Description	High density lipoproteins (HDL) promote homeostasis and counteract stressful tissue damage that underlie cardiovascular and other diseases by mediating reverse cholesterol transport, reducing inflammation, and abrogating oxidative damage. However, metabolically stressful conditions associated with atherosclerosis can impair these effects. Hepatocytes play a major role in the genesis and maturation of circulating HDL. Liver stress elicits marked regulatory changes to circulating HDL abundance and composition, which affect its functionality. Mechanisms linking liver stress to HDL functionality are incompletely understood. In this study, we sought to determine whether stress defending transcription factors nuclear factor erythroid 2 related factor-1 (NRF1) and -2 (NRF2) promote hepatocyte production of functional HDL. Using genetically engineered mouse models briefly fed a mild metabolically stressful diet, we investigated the effect of hepatocyte-specific deletion of NRF1, NRF2, or both on circulating HDL cholesterol level, protein composition, and function. Combined deletion, but not single gene deletion, reduced HDL cholesterol content as well as the capacity of HDL to accept cholesterol efflux from cultured macrophages and to counteract tumor necrosis factor a-induced inflammatory effect on cultured endothelial cells. This coincided with substantial alteration to the circulating HDL proteome, which correlated with liver gene expression profiles of corresponding proteins. Altogether, our findings show complementary actions by hepatocyte NRF1 and NRF2 play a role in shaping HDL composition and promote production of functionally viable HDL. Consequently, our study illuminates the possibility that enhancing stress defense programming in the liver may improve atheroprotective and perhaps other health promoting actions of HDL.
HostingRepository	PRIDE
AnnounceDate	2023-07-03
AnnouncementXML	Submission_2023-07-03_09:27:29.427.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	SadhnaPhanse
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2023-05-09 20:23:20	ID requested
⏵ 1	2023-07-03 09:27:29	announced

Dataset with its publication pending

submitter keyword: high density lipoprotein

liver stress defense

cholesterol

transcription factor

immunometabolism

Scott Widenmaier,PhD
contact affiliation	University of Saskatchewan
contact email	scott.widenmaier@usask.ca
lab head
SadhnaPhanse
contact affiliation	University of Toronto; University of Regina
contact email	srphanse@gmail.com
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD042103
     1. Label: PRIDE project
     2. Name: HDL functionality is dependent on hepatocyte stress defense factors NRF1 and NRF2