Regulation of phosphatidylcholine-derived signaling during oxidative stress. Participation of synaptic membrane rafts

MATEOS, M.V.; SALVADOR, G.A.; GIUSTO, N.M.

Florencia

Congreso; 8th IBRO World Congress of Neuroscience; 2011

International Brain Research Organization (IBRO)

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 (4-month old) and aged rats (28-month old) (Mateos et al., 2008). This lipid messenger can be generated from PC either by a PC-specific phospholipase C (PC-PLC) or through the action of phospholipase D (PLD). In this work the mechanisms that govern synaptic DAG signaling during oxidative injury were studied.  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 and aged rats.  In aged animals, PKC and ERK inhibition showed to decrease DAG generation induced by oxidative injury. The co-localization of PLD1 and PC-PLC with flotillin-1 (a membrane rafts marker), and the DAG generation were not affected neither by aging nor by oxidative stress in isolated membrane rafts (MR). In the presence of iron, lipid peroxidation levels (measured as malondialdehyde formation) were increased in synaptic membranes from adult and aged rats. However, this iron-induced increase in lipid peroxides observed in Syn was absent in MR. This phenomenon was in accordance with a decreased polyunsaturated fatty acid composition in MR with respect to Syn. Our results show that during oxidative injury: a) PC hydrolysis is differentially regulated by aging and b) PC-PLC and PLD1 localization in MR could be a mechanism for preventing DAG rise.