title: Dopaminergic Neurons Respond to Iron-Induced Oxidative Stress by Modulating Lipid Acylation and Deacylation Cycles.
abstract: Metal-imbalance has been reported as a contributor factor for the degeneration of dopaminergic neurons in Parkinson Disease (PD). Specifically, iron (Fe)-overload and copper (Cu) mis-compartmentalization have been reported to be involved in the injury of dopaminergic neurons in this pathology. The aim of this work was to characterize the mechanisms of membrane repair by studying lipid acylation and deacylation reactions and their role in oxidative injury in N27 dopaminergic neurons exposed to Fe-overload and Cu-supplementation. N27 dopaminergic neurons incubated with Fe (1 mM) for 24 hs displayed increased levels of reactive oxygen species (ROS), lipid peroxidation and elevated plasma membrane permeability. Cu-supplemented neurons (10, 50 μM) showed no evidence of oxidative stress markers. A different lipid acylation profile was observed in N27 neurons pre-labeled with [3H] arachidonic acid (AA) or [3H] oleic acid (OA). In Fe-exposed neurons, AA uptake was 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 in TAG. Lipid acylation profile in Cu-supplemented neurons showed AA accumulation into phosphatidylserine and no changes in TAG. The inhibition of deacylation/acylation reactions prompted an increase in oxidative stress markers and mitochondrial dysfunction in Fe-overloaded neurons. These findings provide evidence about the participation of lipid acylation mechanisms against Fe-induced oxidative injury and postulate that dopaminergic neurons cleverly preserve AA in TAG in response to oxidative stress.
authors.affiliation: Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Universidad Nacional del Sur (UNS) and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca, Argentina.
authors.forename: Sofía
authors.initials: S
authors.lastname: Sánchez Campos
authors.affiliation: Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Universidad Nacional del Sur (UNS) and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca, Argentina.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Rodríguez Diez
authors.affiliation: Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Universidad Nacional del Sur (UNS) and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca, Argentina.
authors.forename: Gerardo Martín
authors.initials: GM
authors.lastname: Oresti
authors.affiliation: Instituto de Investigaciones Bioquímicas de Bahía Blanca (INIBIBB), Universidad Nacional del Sur (UNS) and Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Bahía Blanca, Argentina.
authors.forename: Gabriela Alejandra
authors.initials: GA
authors.lastname: Salvador
mesh_terms: D000215:Acylation / Q000502:physiology*; D000818:Animals; D016718:Arachidonic Acid / Q000737:chemistry; D002460:Cell Line; D003300:Copper / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000502:physiology*; D007501:Iron / Q000378:metabolism; D019190:Iron Overload / Q000503:physiopathology*; D050356:Lipid Metabolism / Q000502:physiology*; D015227:Lipid Peroxidation / Q000502:physiology; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D008928:Mitochondria / Q000502:physiology; D019301:Oleic Acid / Q000737:chemistry; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000502:physiology*; D010300:Parkinson Disease / Q000473:pathology; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism
chemical_list: D010743:Phospholipids; D017382:Reactive Oxygen Species; D014280:Triglycerides; D016718:Arachidonic Acid; D019301:Oleic Acid; D003300:Copper; D007501:Iron