Triacylglycerol accumulation and oxidative stress in dopaminergic neurons. Protective role of α-synuclein?

SÁNCHEZ CAMPOS, S.; SALVADOR, G.A.

Puerto Iguazú

Conferencia; 56th International Conference on the Bioscience of Lipids; 2015

Pathological α-synuclein (α-syn) aggregation and iron-induced oxidative stress are involved in the death of dopaminergic neurons in Parkinson Disease (PD). In this work, we characterized the role of lipid acylation/deacylation processes in N27 dopaminergic neurons (WT) and in neurons stably expressing A53T α-syn (a dominant mutation found in familial early onset PD) exposed to iron-induced injury.N27 dopaminergic neurons incubated with iron for 24 hs (Fe, 1mM) displayed increased levels of reactive oxygen species (ROS), lipid peroxidation and elevated plasma membrane permeability. WT neurons also respond to oxidative stress by increasing arachidonic acid acylation in the triacylglycerol (TAG) fraction and oleic acid acylation in phospholipids (PL). We also observed an increase in TAG content and the accumulation of lipid bodies, with augmented Perilipin-2 mRNA levels. The inhibition of PL and cholesterol acylation increased TAG levels and also neuronal susceptibility to oxidative stress.A53T α-syn cells exposed to iron-induced injury, showed lower ROS and lipid peroxide levels than WT neurons. In spite of the decreased oxidative stress markers, A53T α-syn neurons accumulate the highest levels of TAG. A53T α-syn neurons also showed increased levels of fatty acid synthase (FAS) and lysophospholipid acyltransferase (LPAT) expression. Pharmacological inhibition of phospholipid and cholesterol acylation (CI-976) provoked an increase in the accumulation of total TAG content in all the experimental conditions, except in iron exposed A53T α-syn neurons.Based on the experimental evidence presented here, we propose α-syn as a modulator of oxidative stress and lipid metabolism in an in vitro model of PD.