Atg5 deficit exaggerates the lysosome formation and cathepsin B activation in mice brain after lipid nanoparticles injection.
Nanomedicine
; 10(8): 1843-52, 2014 Nov.
Article
em En
| MEDLINE
| ID: mdl-24768629
ABSTRACT
The present study was designed to investigate the role of autophagy-lysosome signaling in the brain after application of nanoparticles. Here, lipid nanoparticles (LNs) induced elevations of Atg5, P62, LC3 and cathepsin B in mice brain. The transmission electron microscopy revealed a dramatic elevation of lysosome vacuoles colocalized with LNs cluster inside the neurons in mice brain. Immunoblot data revealed abnormal expression of cathepsin B in brain cortex following LNs injection, whereas its expression was further elevated in Atg5(+/-) mice. The importance of Atg5 in the LNs-induced autophagy-lysosome cascade was further supported by our finding that neurovascular response was exaggerated in Atg5(+/-) mice. In addition, the siRNA knockdown of Atg5 significantly blunted the increasing of LC3 and P62 in LNs-treated Neuro-2a cells. Taken together, we propose that LNs induce autophagy-lysosome signaling and neurovascular response at least partially via an Atg5-dependent pathway. FROM THE CLINICAL EDITOR These authors investigated autophagy-lysosome signaling in the mouse brain after application of lipid nanoparticles and report that these nanoparticles induce autophagy-lysosome signaling and neurovascular response at least partially via an Atg5-dependent pathway.
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Base de dados:
MEDLINE
Assunto principal:
Encéfalo
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Catepsina B
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Nanopartículas
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Lipídeos
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Lisossomos
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Proteínas Associadas aos Microtúbulos
Limite:
Animals
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article