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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

dc.contributor.author	Ibáñez Cabellos, José Santiago
dc.contributor.author	Aguado Muñoz, Carmen
dc.contributor.author	Pérez Cremades, Daniel
dc.contributor.author	García-Giménez, José 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.citation	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.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.subject	Fisiologia
dc.title	Extracellular histones activate autophagy and apoptosis via mTOR signaling in human endothelial cells
dc.type	journal article	es_ES
dc.date.updated	2021-09-06T07:49:29Z
dc.identifier.doi	10.1016/j.bbadis.2018.07.010
dc.identifier.idgrec	130186
dc.rights.accessRights	open access	es_ES