PXD030565

PXD030565 is an original dataset announced via ProteomeXchange.

Title	Changes in endothelial cell secretome after sirtuin-1 knock-down
Description	Sirtuin1 (Sirt1) in skeletal muscle (SK) and fat protects against metabolic damage by stimulating insulin sensitivity. Here we report that mice with selective deletion of endothelial Sirt1 (E-Sirt1-KO) paradoxically exhibit heightened whole-body insulin sensitivity. Akt phosphorylation, glucose uptake, and glycolysis are boosted in SK and brown adipose tissue (BAT) of E-Sirt1-KO mice. E-Sirt1-KO mice have higher energy expenditure and are partially protected from high-fat diet-induced insulin resistance. Enhanced insulin sensitivity and peripheral tissue Akt phosphorylation in E-Sirt1-KO mice is transferrable to wild-type mice via the systemic circulation after surgical parabiosis. Silencing of Sirt1 in endothelial cells upregulates transcription of the F-actin-binding protein thymosin beta-4 (Tβ4), whose secretion activates Akt in skeletal myotubes. Sirt1 downregulation stimulates endothelial Tβ4 transcription through inhibition of autophagy and upregulation of nuclear factor-kappa B signaling. Thus, unlike Sirt1 in skeletal muscle and fat, endothelial Sirt1 curtails whole-body insulin sensitivity by inhibiting expression of secreted Tβ4.
HostingRepository	PRIDE
AnnounceDate	2023-08-07
AnnouncementXML	Submission_2023-08-06_18:05:16.446.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	MarkusBachschmid
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-21 03:18:10	ID requested
⏵ 1	2023-08-06 18:05:16	announced

Dataset with its publication pending

submitter keyword: SirT1,HUVEC, Secretome

KailkobadIrani
contact affiliation	Division of Cardiovascular Medicine, Department of Medicine, Abboud Cardiovascular Research Center, University of Iowa Carver College of Medicine, Iowa City, Iowa, USA. Fraternal Order of Eagles Diabetes Research Center, Pappajohn Biomedical Institute, and Heart and Vascular Center, University of Iowa, University of Iowa, Iowa City, Iowa, USA.
contact email	kaikobad-irani@uiowa.edu
lab head
MarkusBachschmid
contact affiliation	Quintara Biosciences
contact email	bachschmid.markus@gmail.com
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/2023/08/PXD030565

PRIDE project URI

• PRIDE
  1. PXD030565
     1. Label: PRIDE project
     2. Name: Changes in endothelial cell secretome after sirtuin-1 knock-down