Lysosomal dysfunction induced cytosolic vacuolation and increased intracellular amyloid-beta 42 (Aβ42) in human brain endothelial cells (HBEC-5i)

Lysosome is a primary degradative organelle and is crucial in cellular homeostasis. A reduction in its function due to ageing has been associated with the development of Alzheimer's disease (AD), a common neurodegenerative disorder characterised by the deposition of neurotoxic amyloid plaque in...

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Bibliographic Details
Published in:Biomedicine & pharmacotherapy 2023-05, Vol.161, p.114501-114501, Article 114501
Main Authors: Laili, Iffah Nadiah, Nasir, Mohd Hamzah Mohd, Jufri, Nurul Farhana, Ibrahim, Farah Wahida, Hamid, Asmah
Format: Article
Language:English
Subjects:
Alzheimer Disease - metabolism
Alzheimer’s disease
Amyloid angiopathy
Amyloid beta-Peptides - metabolism
Autophagic vacuoles
Brain - metabolism
Cytosol - metabolism
Disease Progression
Endothelial Cells - metabolism
Humans
Lysosome inhibitor
Lysosomes - metabolism
Neurodegenerative diseases
Neurovascular dysfunction
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Summary:Lysosome is a primary degradative organelle and is crucial in cellular homeostasis. A reduction in its function due to ageing has been associated with the development of Alzheimer's disease (AD), a common neurodegenerative disorder characterised by the deposition of neurotoxic amyloid plaque in the brain and cerebral vessel walls. The breakdown of the blood-brain barrier (BBB) plays a vital role in the pathogenesis of AD. However, the impact of lysosomal dysfunction on brain endothelial cells, the key component of the BBB, in the disease progression is yet to be fully understood. In this study, human brain endothelial cells (HBEC-5i) were exposed to a lysosomotropic compound, chloroquine (CQ) for 24 h. Cell viability was assessed with the 3-(4,5-dimethylthiazol-2-yl)− 2,5-diphenyltetrazolium bromide (MTT) assay to determine the inhibitory concentration (IC) at IC10 (17.5 µM), IC25 (70.5 µM), and IC50 (125 µM). The morphological changes observed include vacuoles arrested in the cytosols and cell shrinkage that were more prominent at IC25 and IC50. Lysosomal dysfunction was evaluated by measuring the lysosomal-associated membrane protein-1 (LAMP-1) and microtubule-associated protein light chain 3-II (LC3-II) using the capillary-based immunoassay. LC3-II was significantly increased at IC25 and IC50 (p 
ISSN:0753-3322
1950-6007
DOI:10.1016/j.biopha.2023.114501