Intracellular functions of low molecular weight phospholipases A2

Mammalian neural cells express various isoforms of low molecular weight (13–18 kDa) phospholipases A2 which participate to cell signalling by producing lipid mediators, but are also involved in neurodegeneration. Exogenous sPLA2, added to neuronal cells in culture, release neurotransmitters and potentiate the neurotoxic effects of glutamate (Kolko et al. J. Biol. Chem. 271: 32722–32728, 1996). Recent observations have attracted the interest to other roles of sPLA2 in intracellular mechanisms. Indeed, GIIA sPLA2 is present in rat brain cortex mitochondria and it has been proposed its involvement in cell death because it is released under reduced membrane potential (Macchioni et al. J. Biol. Chem. 279: 37860– 37869, 2004). Another isoform (GV) is localized in the nuclei of cultured cells and also detected in nuclei of rat cerebral cortex (Nardicchi et al. Biochim. Biophys. Acta. 1771: 1345–1352, 2007). The nuclear function of this isoform is completely unknown. Endogenous GIIA sPLA2 is also involved in neuritogenesis because it accumulates into growth cones and neurite tips when PC12 cells are differentiated by NGF. The participation to membrane remod- eling during neuritogenesis represents one of the intracellular functions of neuronal of GIIA-sPLA2 together with the removal of oxidized fatty acid from phospholipids under normal respiratory conditions, because of the low specificity for fatty acids of this isoform. Increased expression of GIIA and/or its activation takes place during oxidative stress and lead to cell death very likely because of the release of cyt c by a mechanism involving mitochondrial GIIA. In order to get more insight the functional and pathological roles of this enzyme, a specific antibody has been obtained by a new methodology.