INVESTIGADORES
SALVADOR Gabriela Alejandra
artículos
Título:
Dopaminergic Neurons Respond to Iron-Induced Oxidative Stress by Modulating Lipid Acylation and Deacylation Cycles
Autor/es:
SANCHEZ CAMPOS, S; RODRIGUEZ DIEZ, G; ORESTI, M.; SALVADOR, G. AUTOR CORRESP.
Revista:
PLOS ONE
Editorial:
PUBLIC LIBRARY SCIENCE
Referencias:
Lugar: San Francisco; Año: 2015 vol. 10
ISSN:
1932-6203
Resumen:
Metal-imbalance has been reported as a contributor factor for the degeneration of dopaminergicneurons in Parkinson Disease (PD). Specifically, iron (Fe)-overload and copper (Cu)mis-compartmentalization have been reported to be involved in the injury of dopaminergicneurons in this pathology. The aim of this work was to characterize the mechanisms ofmembrane repair by studying lipid acylation and deacylation reactions and their role in oxidativeinjury in N27 dopaminergic neurons exposed to Fe-overload and Cu-supplementation.N27 dopaminergic neurons incubated with Fe (1mM) for 24 hs displayed increasedlevels of reactive oxygen species (ROS), lipid peroxidation and elevated plasma membranepermeability. Cu-supplemented neurons (10, 50 μM) showed no evidence of oxidativestress markers. A different lipid acylation profile was observed in N27 neurons pre-labeledwith [3H] arachidonic acid (AA) or [3H] oleic acid (OA). In Fe-exposed neurons, AA uptakewas increased in triacylglycerols (TAG) whereas its incorporation into the phospholipid (PL)fraction was diminished. TAG content was 40% higher in Fe-exposed neurons than in controls.This increase was accompanied by the appearance of Nile red positive lipid bodies.Contrariwise, OA incorporation increased in the PL fractions and showed no changes inTAG. Lipid acylation profile in Cu-supplemented neurons showed AA accumulation intophosphatidylserine and no changes in TAG. The inhibition of deacylation/acylation reactionsprompted an increase in oxidative stress markers and mitochondrial dysfunction in Feoverloadedneurons. These findings provide evidence about the participation of lipid acylationmechanisms against Fe-induced oxidative injury and postulate that dopaminergic neuronscleverly preserve AA in TAG in response to oxidative stress.
