DJ-1 interacts with the ectopic ATP-synthase in endothelial cells during acute ischemia and reperfusion
Gallinat, Alex (Institut d'Investigació Biomèdica Sant Pau)
Badimon, Lina (Institut d'Investigació Biomèdica Sant Pau)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	Endothelial cells (ECs) play a central role in ischemia. ATP-Synthase is now recognized to be ectopically expressed in the cell surface of many cell types, with putative roles described in angiogenesis, proliferation, and intracellular pH regulation. DJ-1 is a multifunctional protein, involved in cell protection against ischemia, ischemia-reperfusion (I/R), and oxidative stress, that regulates mitochondrial ATP-synthase. Here we focused on the characterization of the endothelial dynamics of DJ-1, and its implication in the regulation of the ectopic ATP-synthase (ecATP-S) activity, during acute ischemia and I/R in ECs. We found that DJ-1 is secreted from ECs, by a mechanism enhanced in ischemia and I/R. A cleaved form of DJ-1 (DJ-1∆C) was found only in the secretome of ischemic cells. The ecATP-S activity increased following acute ischemia in ECs, coinciding with DJ-1 and DJ-1∆C secretion. The inhibition of DJ-1 expression inhibited the ecATP-S response to ischemia by ∼ 50%, and its exogenous administration maximized the effect, together with an enhanced Akt phosphorylation and angiotube-formation potential at reperfusion. Immunoprecipitation studies showed direct interaction between DJ-1 and the ecATP-S. Altogether suggesting that DJ-1 is actively cleaved and released from ischemic ECs and plays an important role in the regulation of the ecATP-S activity during acute ischemia and reperfusion.
Grants:	Agencia Estatal de Investigación PID2019-107160RB-I00 Instituto de Salud Carlos III 2020-023/AC209-00054
Note:	Altres ajuts: Ministerio de Ciencia e Innovación. BES Pre-doctoral fellowship (BES-2017-081378).
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Adenosine Triphosphate ; Endothelial Cells ; Humans ; Ischemia ; Myocardial Reperfusion Injury ; Protein Deglycase DJ-1 ; Reperfusion
Published in:	Scientific reports, Vol. 12 Núm. 1 (december 2022) , p. 12753, ISSN 2045-2322

DOI: 10.1038/s41598-022-16998-3
PMID: 35882968

12 p, 2.1 MB

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Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Recerca Sant Pau
Articles > Research articles
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