Extracellular histones activate autophagy and apoptosis via mTOR signaling in human endothelial cells
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Extracellular histones activate autophagy and apoptosis via mTOR signaling in human endothelial cells

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Extracellular histones activate autophagy and apoptosis via mTOR signaling in human endothelial cells

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dc.contributor.author Ibáñez Cabellos, Jose Santiago
dc.contributor.author Aguado, Carmen
dc.contributor.author Pérez Cremades, Daniel
dc.contributor.author García-Giménez, Jose Luis
dc.contributor.author Bueno Betí, Carlos
dc.contributor.author García-López, Eva M.
dc.contributor.author Romá-Mateo, Carlos
dc.contributor.author Novella, Susana
dc.contributor.author Hermenegildo, Carlos
dc.contributor.author Pallardó, Federico V.
dc.date.accessioned 2021-09-06T07:49:28Z
dc.date.available 2021-09-06T07:49:28Z
dc.date.issued 2018
dc.identifier.uri https://hdl.handle.net/10550/80243
dc.description.abstract Circulating histones have been proposed as targets for therapy in sepsis and hyperinflammatory symptoms. However, the proposed strategies have failed in clinical trials. Although different mechanisms for histone-related cytotoxicity are being explored, those mediated by circulating histones are not fully understood. Extracellular histones induce endothelial cell death, thereby contributing to the pathogenesis of complex diseases such as sepsis and septic shock. Therefore, the comprehension of cellular responses triggered by histones is capital to design effective therapeutic strategies. Here we report how extracellular histones induce autophagy and apoptosis in a dose-dependent manner in cultured human endothelial cells. In addition, we describe how histones regulate these pathways via Sestrin2/AMPK/ULK1-mTOR and AKT/mTOR. Furthermore, we evaluate the effect of Toll-like receptors in mediating autophagy and apoptosis demonstrating how TLR inhibitors do not prevent apoptosis and/or autophagy induced by histones. Our results confirm that histones and autophagic pathways can be considered as novel targets to design therapeutic strategies in endothelial damage.
dc.language.iso eng
dc.relation.ispartof Biochimica et Biophysica Acta-Molecular Basis of Disease, 2018, vol. 1864, p. 3234-3246
dc.rights.uri info:eu-repo/semantics/openAccess
dc.source Ibáñez Cabellos, Jose Santiago Aguado, Carmen Pérez Cremades, Daniel García-Giménez, Jose Luis Bueno Betí, Carlos García-López, Eva M. Romá-Mateo, Carlos Novella, Susana Hermenegildo, Carlos Pallardó, Federico V. 2018 Extracellular histones activate autophagy and apoptosis via mTOR signaling in human endothelial cells Biochimica et Biophysica Acta-Molecular Basis of Disease 1864 3234 3246
dc.subject Fisiologia
dc.title Extracellular histones activate autophagy and apoptosis via mTOR signaling in human endothelial cells
dc.type info:eu-repo/semantics/article
dc.date.updated 2021-09-06T07:49:29Z
dc.identifier.doi https://doi.org/10.1016/j.bbadis.2018.07.010
dc.identifier.idgrec 130186

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