PXD018969-1

PXD018969 is an original dataset announced via ProteomeXchange.

Title	Keap1 governs ageing-induced protein aggregation in endothelial cells
Description	The breach of proteostasis, leading to the accumulation of protein aggregates, is a hallmark of ageing and age-associated disorders, up to now well-established in neurodegeneration. Few studies have addressed the issue of dysfunctional cell response to protein deposition also for the cardiovascular system. However, the molecular basis of proteostasis decline in vascular cells, as well as its relation to ageing, are not understood. Recent studies have indicated the associations of Nrf2 transcription factor, the critical modulator of cellular stress-response, with ageing and premature senescence. In this report, we outline the significance of protein aggregation in physiological and premature ageing of murine and human endothelial cells (ECs). Our study shows that aged donor-derived and prematurely senescent Nrf2-deficient primary human ECs, but not those overexpressing dominant-negative Nrf2, exhibit increased accumulation of protein aggregates. Such phenotype is also found in the aortas of aged mice and young Nrf2 tKO mice. Ageing-related loss of proteostasis in ECs depends on Keap1, well-known repressor of Nrf2, recently perceived as a key independent regulator of EC function. Ageing-induced deposition of protein aggregates in ECs is associated with impaired autophagy and can be counteracted by Keap1 depletion or rapamycin treatment. Our results show that Keap1:Nrf2 protein balance predominates Nrf2 transcription-dependent mechanisms in governing proteostasis and ageing in ECs.
HostingRepository	PRIDE
AnnounceDate	2020-08-12
AnnouncementXML	Submission_2020-08-12_00:07:44.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Dominik Cysewski
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	2020-05-04 03:33:44	ID requested
⏵ 1	2020-08-12 00:07:45	announced

Kopacz A, Kloska D, Targosz-Korecka M, Zapotoczny B, Cysewski D, Personnic N, Werner E, Hajduk K, Jozkowicz A, Grochot-Przeczek A, Keap1 governs ageing-induced protein aggregation in endothelial cells. Redox Biol, 34():101572(2020) [pubmed]

submitter keyword: human, aggregates, Keap1,

Anna Grochot-Przęczek
contact affiliation	Department of Medical Biotechnology Faculty of Biochemistry, Biophysics and Biotechnology Jagiellonian University Gronostajowa 7 30-387 Krakow, Poland
contact email	anna.grochot-przeczek@uj.edu.pl
lab head
Dominik Cysewski
contact affiliation	Institute of Biochemistry and Biophysics Polish Academy of Sciences
contact email	dominikcysewski@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/2020/08/PXD018969

PRIDE project URI

• PRIDE
  1. PXD018969
     1. Label: PRIDE project
     2. Name: Keap1 governs ageing-induced protein aggregation in endothelial cells