DJ-1 interacts with the ectopic ATP-synthase in endothelial cells during acute ischemia and reperfusion
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 ce...
| Authors: | , |
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| Format: | article |
| Status: | Published version |
| Publication Date: | 2022 |
| Country: | España |
| Institution: | Institut d’Investigació Biomèdica Sant Pau (IIB Sant Pau) |
| Repository: | r-IIB SANT PAU. Repositorio Institucional de Producción Científica del Instituto de Investigación Biomédica Sant Pau |
| OAI Identifier: | oai:iibsantpau.fundanetsuite.com:p12287 |
| Online Access: | https://iibsantpau.fundanetsuite.com/Publicaciones/ProdCientif/PublicacionFrw.aspx?id=12287 https://ddd.uab.cat/record/280888 |
| Access Level: | Open access |
| Keyword: | adenosine triphosphate protein deglycase DJ-1 endothelium cell genetics human ischemia metabolism myocardial ischemia reperfusion injury reperfusion Adenosine Triphosphate Endothelial Cells Humans Ischemia Myocardial Reperfusion Injury Protein Deglycase DJ-1 Reperfusion |
| Summary: | 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 increment 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 increment C secretion. The inhibition of DJ-1 expression inhibited the ecATP-S response to ischemia by similar to 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. |
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