Impairment of the autophagic flux in astrocytes intoxicated by trimethyltin

Cinzia Fabrizi, Elena Pompili, Stefania De Vito, Francesca Somma, Angela Catizone, Giulia Ricci, Paola Lenzi, Francesco Fornai, Lorenzo Fumagalli

Research output: Contribution to journalArticle

Abstract

Autophagy is a lysosomal catabolic route for protein aggregates and damaged organelles which in different stress conditions, such as starvation, generally improves cell survival. An impairment of this degradation pathway has been reported to occur in many neurodegenerative processes. Trimethyltin (TMT) is a potent neurotoxin present as an environmental contaminant causing tremors, seizures and learning impairment in intoxicated subjects. The present data show that in rat primary astrocytes autophagic vesicles (AVs) appeared after few hours of TMT treatment. The analysis of the autophagic flux in TMT-treated astrocytes was consistent with a block of the late stages of autophagy and was accompanied by a progressive accumulation of the microtubule associated protein light chain 3 (LC3) and of p62/SQSTM1. Interestingly, an increased immunoreactivity for p62/SQSTM1 was also observed in hippocampal astrocytes detected in brain slices of TMT-intoxicated rats. The time-lapse recordings of AVs in EGFP-mCherry-LC3B transfected astrocytes demonstrated a reduced mobility of autophagosomes after TMT exposure respect to control cells. The observed block of the autophagic flux cannot be overcome by known autophagy inducers such as rapamycin or 0.5. mM lithium. Although ineffective when used at 0.5. mM, lithium at higher concentrations (2. mM) was able to protect astrocyte cultures from TMT toxicity. This effect correlated well with its ability to determine the phosphorylation/inactivation of glycogen kinase synthase-3β (GSK-3β).

Original languageEnglish
Pages (from-to)12-22
Number of pages11
JournalNeuroToxicology
Volume52
DOIs
Publication statusPublished - Jan 1 2016

Fingerprint

Astrocytes
Fluxes
Autophagy
Glycogen Synthase Kinase 3
Lithium
Rats
Phosphorylation
Aptitude
Microtubule-Associated Proteins
Neurotoxins
Tremor
Sirolimus
Starvation
Organelles
Toxicity
trimethyltin
Brain
Cell Survival
Seizures
Cells

Keywords

  • Astrocytes
  • Autophagy
  • Lithium
  • Neurodegeneration
  • Trimethyltin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Toxicology

Cite this

Fabrizi, C., Pompili, E., De Vito, S., Somma, F., Catizone, A., Ricci, G., ... Fumagalli, L. (2016). Impairment of the autophagic flux in astrocytes intoxicated by trimethyltin. NeuroToxicology, 52, 12-22. https://doi.org/10.1016/j.neuro.2015.10.004

Impairment of the autophagic flux in astrocytes intoxicated by trimethyltin. / Fabrizi, Cinzia; Pompili, Elena; De Vito, Stefania; Somma, Francesca; Catizone, Angela; Ricci, Giulia; Lenzi, Paola; Fornai, Francesco; Fumagalli, Lorenzo.

In: NeuroToxicology, Vol. 52, 01.01.2016, p. 12-22.

Research output: Contribution to journalArticle

Fabrizi, C, Pompili, E, De Vito, S, Somma, F, Catizone, A, Ricci, G, Lenzi, P, Fornai, F & Fumagalli, L 2016, 'Impairment of the autophagic flux in astrocytes intoxicated by trimethyltin', NeuroToxicology, vol. 52, pp. 12-22. https://doi.org/10.1016/j.neuro.2015.10.004
Fabrizi C, Pompili E, De Vito S, Somma F, Catizone A, Ricci G et al. Impairment of the autophagic flux in astrocytes intoxicated by trimethyltin. NeuroToxicology. 2016 Jan 1;52:12-22. https://doi.org/10.1016/j.neuro.2015.10.004
Fabrizi, Cinzia ; Pompili, Elena ; De Vito, Stefania ; Somma, Francesca ; Catizone, Angela ; Ricci, Giulia ; Lenzi, Paola ; Fornai, Francesco ; Fumagalli, Lorenzo. / Impairment of the autophagic flux in astrocytes intoxicated by trimethyltin. In: NeuroToxicology. 2016 ; Vol. 52. pp. 12-22.
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