Atg5 deficit exaggerates the lysosome formation and cathepsin B activation in mice brain after lipid nanoparticles injection

Nan Nan Lu, Jun Liu, Yun Tian, Mei Hua Liao, Huan Wang, Ying Mei Lu, Rong Rong Tao, Ling Juan Hong, Shuang Shuang Liu, Kohji Fukunaga, Yong Zhong Du, Feng Han

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1843-1852
Number of pages10
JournalNanomedicine: Nanotechnology, Biology, and Medicine
Volume10
Issue number8
DOIs
Publication statusPublished - 2014 Nov 1

Keywords

  • Atg5
  • Autophagy
  • Brain
  • Lipid nanoparticles
  • Neurovascular damage

ASJC Scopus subject areas

  • Bioengineering
  • Medicine (miscellaneous)
  • Molecular Medicine
  • Biomedical Engineering
  • Materials Science(all)
  • Pharmaceutical Science

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