Ischemic-reperfusion (I/R) injury induced a remodeling of protein and lipid homeostasis, under oxidative stress and inflammatory status. Starvation occurring during I/R is a condition leading to autophagy activation, which allows abnormal material clearance or amino acid, or both, and fatty acid (FA) recycling essential for survival. This study investigated the lipid reshaping, peroxidation, and related-signaling pathways, in rat brain endothelial cells (RBE4) subjected to 3 h of oxygen and glucose deprivation (OGD) and restoration of standard condition (I/R in vitro model). Lipids and proteins were analyzed after 1 or 24 h of oxygen and nutrient restoration. Together with the oxidative stress and inflammatory status, I/R injury induced a reshaping of neutral lipids and biogenesis of lipid droplets (LD) with excessive lipid storage. The increase of LC3-II/LC3-I ratio, an autophagy marker, and LC3 co-localization with LD suggest the activation of lipophagy machinery to counteract the cell engulfment. Lipophagy leads to cholesterol ester (CE) hydrolysis, increasing free cholesterol (FC) secretion, which occurred by specific transporters or unconventional exocytosis pathways, or both. Here, we propose that an unconventional spreading of FC and other lipid metabolites may influence the neurovascular unit (NVU) cells, contributing to Blood brain barrier (BBB) alteration or adaptation, or both, to the cumulative effects of several transient ischemia

Lonati, E., Corsetto, P., Montorfano, G., Zava, S., Carrozzini, T., Brambilla, A., et al. (2019). Lipid reshaping and lipophagy are induced in a modeled ischemia-reperfusion injury of blood brain barrier. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 20(15) [10.3390/ijms20153752].

Lipid reshaping and lipophagy are induced in a modeled ischemia-reperfusion injury of blood brain barrier

Lonati E.;Carrozzini T.;Botto L.;Palestini P.;Bulbarelli A.
2019

Abstract

Ischemic-reperfusion (I/R) injury induced a remodeling of protein and lipid homeostasis, under oxidative stress and inflammatory status. Starvation occurring during I/R is a condition leading to autophagy activation, which allows abnormal material clearance or amino acid, or both, and fatty acid (FA) recycling essential for survival. This study investigated the lipid reshaping, peroxidation, and related-signaling pathways, in rat brain endothelial cells (RBE4) subjected to 3 h of oxygen and glucose deprivation (OGD) and restoration of standard condition (I/R in vitro model). Lipids and proteins were analyzed after 1 or 24 h of oxygen and nutrient restoration. Together with the oxidative stress and inflammatory status, I/R injury induced a reshaping of neutral lipids and biogenesis of lipid droplets (LD) with excessive lipid storage. The increase of LC3-II/LC3-I ratio, an autophagy marker, and LC3 co-localization with LD suggest the activation of lipophagy machinery to counteract the cell engulfment. Lipophagy leads to cholesterol ester (CE) hydrolysis, increasing free cholesterol (FC) secretion, which occurred by specific transporters or unconventional exocytosis pathways, or both. Here, we propose that an unconventional spreading of FC and other lipid metabolites may influence the neurovascular unit (NVU) cells, contributing to Blood brain barrier (BBB) alteration or adaptation, or both, to the cumulative effects of several transient ischemia
Articolo in rivista - Articolo scientifico
cholesterol; ischemia; lipid droplets; lipophagy; oxygen and glucose deprivation; vessel disease
English
2019
20
15
3752
partially_open
Lonati, E., Corsetto, P., Montorfano, G., Zava, S., Carrozzini, T., Brambilla, A., et al. (2019). Lipid reshaping and lipophagy are induced in a modeled ischemia-reperfusion injury of blood brain barrier. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 20(15) [10.3390/ijms20153752].
File in questo prodotto:
File Dimensione Formato  
10281-241494.pdf

accesso aperto

Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Dimensione 3.08 MB
Formato Adobe PDF
3.08 MB Adobe PDF Visualizza/Apri
Bulbarelli A ijms-20-03752.pdf

Solo gestori archivio

Tipologia di allegato: Publisher’s Version (Version of Record, VoR)
Dimensione 3.08 MB
Formato Adobe PDF
3.08 MB Adobe PDF   Visualizza/Apri   Richiedi una copia

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/241494
Citazioni
  • Scopus 17
  • ???jsp.display-item.citation.isi??? 15
Social impact