Age related regulation and compartamentalization of diacylglycerol signaling during oxidative stress

MATEOS, MELINA VALERIA; SALVADOR, GABRIELA ALEJANDRA; GIUSTO, NORMA MARÍA

Puerto Madryn, Chubut

Congreso; XLVI Reunión Anual de la SAIB; 2010

SAIB

We have previously demonstrated that iron-induced oxidative stress  stimulates diacylglycerol (DAG) generation from phosphatidylcholine (PC) in isolated cerebral cortex synaptic endings (Syn) obtained from adult and aged rats (Mateos et al., 2008). This lipid messenger can be generated either by a PC-specific phospholipase C (PC-PLC) or through the action of phospholipase D (PLD). The purpose of this work was to elucidate the regulation mechanisms that govern DAG signaling during oxidative injury.  DAG formation was differentially affected by the use of PIP2-PLC, PKC and ERK kinases inhibitors (U73122, BIM and U0126, respectively). U73122 partially inhibited DAG generation in adult rats.  In aged animals, PKC and ERK inhibition showed to decrease (20 %) DAG generation induced by oxidative injury. The co-localization of PLD1 and PC-PLC with flotillin, and the DAG generation were not affected neither by aging nor by oxidative stress in isolated membrane rafts (MR). In addition, the iron-induced increase in lipid peroxidation levels observed in Syn was absent in MR. The reduced lipid peroxidation levels in MR, were in accordance with a decrease (68%) in polyunsaturated fatty acid composition with respect to Syn. Our results show that during oxidative injury: i) PC hydrolysis is differentially regulated by aging and ii) PC-PLC and PLD compartmentalization could be a mechanism for preventing DAG rise.