Next Article in Journal
Genetic Variants in the Promoter Region of the Macrophage Migration Inhibitory Factor are Associated with the Severity of Hepatitis C Virus-Induced Liver Fibrosis
Next Article in Special Issue
Astaxanthin Ameliorates Ischemic-Hypoxic-Induced Neurotrophin Receptor p75 Upregulation in the Endothelial Cells of Neonatal Mouse Brains
Previous Article in Journal
New Insights about the Wnt/β-Catenin Signaling Pathway in Primary Bone Tumors and Their Microenvironment: A Promising Target to Develop Therapeutic Strategies?
Previous Article in Special Issue
Ureaplasma Species Modulate Cytokine and Chemokine Responses in Human Brain Microvascular Endothelial Cells
Open AccessArticle

Lipid Reshaping and Lipophagy Are Induced in a Modeled Ischemia-Reperfusion Injury of Blood Brain Barrier

1
School of Medicine and Surgery, University of Milano-Bicocca, 20900 Monza, Italy
2
NeuroMi, Milan Center for Neuroscience, University of Milano-Bicocca, San Gerardo Hospital, 20900 Monza, Italy
3
Department of Pharmacological and Biomolecular Sciences, DiSFeB, Università degli Studi di Milano, 20133 Milan, Italy
4
Adienne Srl, 20867 Caponago, MB, Italy
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2019, 20(15), 3752; https://doi.org/10.3390/ijms20153752
Received: 27 June 2019 / Revised: 26 July 2019 / Accepted: 29 July 2019 / Published: 31 July 2019
(This article belongs to the Special Issue Small Vessel Disease: A Whole Brain Disease)
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. View Full-Text
Keywords: oxygen and glucose deprivation; lipophagy; lipid droplets; cholesterol; ischemia; vessel disease oxygen and glucose deprivation; lipophagy; lipid droplets; cholesterol; ischemia; vessel disease
Show Figures

Figure 1

MDPI and ACS Style

Lonati, E.; Corsetto, P.A.; Montorfano, G.; Zava, S.; Carrozzini, T.; Brambilla, A.; Botto, L.; Palestini, P.; Rizzo, A.M.; Bulbarelli, A. Lipid Reshaping and Lipophagy Are Induced in a Modeled Ischemia-Reperfusion Injury of Blood Brain Barrier. Int. J. Mol. Sci. 2019, 20, 3752.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop