Fabrizi, Cinzia

Fornai, Francesca

Fumagalli, Lorenzo

Lenzi, Paola

Nori, Stefania L.

Panetta, Barbara

Pompili, Elena

Somma, Francesca

Firenze University Press: E-Journals

IJAE Vol. 115, n. 1/2 (Supplement), 2010
62
Role of autophagy in trimethyltin intoxication
Cinzia Fabrizi1, Elena Pompili1, Barbara Panetta1, Francesca Somma1, Stefania L. Nori2, Francesco For-
nai3, Paola Lenzi3, Lorenzo Fumagalli1
1 Department of Human Anatomy, University of Rome “La Sapienza”, Italy
2 Department of Pharmaceutical Sciences, University of Salerno, Italy
3 Department of Human Morphology and Applied Biology, University of Pisa, Italy
The great impact of trimethyltin (TMT) on human health is due to the widespread 
occurrence of methyltin compounds which are widely used as fungicides and chemosta-
bilizers. TMT is known to cause neuronal degeneration in the central nervous system 
involving primarily the limbic system.
After TMT intoxication, increased autophagic activity is observed in neurons both in 
humans and in animal models. Autophagy is a process of bulk degradation of cellular 
constituents through an autophagosomic-lysosomal pathway. Its contribution to pro-
survival or pro-death mechanisms in neurodegenerative diseases is still controversial.
When rodents hippocampal neuronal cultures and PC12 cells are treated with TMT, 
an increased cytotoxicity is observed by LDH release, MTT test and cell counts. Lithium 
is commonly used as mood stabilizer and exhibits neuroprotective properties against an 
array of insults in vivo and in vitro. The beneficial effects of lithium are thought to be 
due to the inhibition of the glycogen synthase kinase-3beta (GSK-3beta) and the deple-
tion of the intracellular inositol pool via the inhibition of various enzymes in the pos-
phoinositide pathways, such as the rate-limiting enzyme inositol monophosphatase-1 
(IMPase-1). Through the inhibition of IMPase-1 lithium is known to promote autophagy. 
Our results show that low concentrations of lithium (0.5-1 mM) protect neuronal cells 
from TMT-induced cell death while higher concentrations (above 2 mM) display direct 
toxicity in our cultures. TMT toxicity is accompanied by the formation of numerous 
and large acidic vacuoles stained by monodansylcadaverine. Moreover, if in these cells 
autophagy is inhibited by 3-methyladenine or asparagine TMT-induced toxicity is en-
hanced.
Key words
Autophagy, lithium, trimethyltin, neurodegenerative diseases


Role of autophagy in trimethyltin intoxication

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Role of autophagy in trimethyltin intoxication

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