NGF Induces the Expression of Group IIA Secretory Phospholipase A2 in PC12 Cells: The Newly Synthesized Enzyme Is Addressed to Growing Neurites

Abstract

We proposed that group IIA secretory phospholipase A(2) (GIIA) participates in neuritogenesis based on our observations that the enzyme migrates to growth cones and neurite tips when PC12 cells are induced to differentiate by nerve growth factor (NGF) (Ferrini et al., Neurochem Res 35:2168-2174, 2010). The involvement of other secretory PLA(2) isoforms in neuronal development has been suggested by others but through different mechanisms. In the present study, we compared the subcellular distribution of GIIA and group X sPLA(2) (GX) after stimulation of PC12 cells with NGF. We found that GIIA, but not GX, localized at the neuritic tips after treatment with NGF, as demonstrated by immunofluorescence analysis. We also found that NGF stimulated the expression and the activity of GIIA. In addition, NGF induced the expressed myc-tagged GIIA protein to migrate to neurite tips in its active form. We propose that GIIA expression, activity, and subcellular localization is regulated by NGF and that the enzyme may participate in neuritogenesis through intracellular mechanisms, most likely by facilitating the remodelling of glycerophospholipid molecular species by deacylation-reacylation reactions necessary for the incorporation of polyunsaturated fatty acids.

The Effect of Resveratrol on the Composition and State of Lipids and the Activity of Phospholipase A2 During the Excitation and Regeneration of Somatic Nerves

“…It is likely that the accumulation of lysophospholipids during nerve damage is due to an increase in the activity of PL A 2 , which catalyzes the hydrolysis of phospholipids of polyunsaturated FA (Isakina et al, 2015). This has been evidenced by data on the participation of PL A 2 in the process of early myelin degradation during Waller’ degeneration of rat and mouse nerves and frog sciatic nerves (Nardicchi et al, 2014; Revin et al, 2015). Not only the lysophospholipids but also the FFA have a detergent effect and are powerful regulators of physiological and biochemical processes.…”

“…The aim of our study was to investigate the composition and condition of lipids changes during the somatic nerves excitation and damage. The enzyme phospholipase A 2 , especially Ca 2+ -dependent phospholipase A 2 , plays an important role in the study of lipid composition (O’Donoghue et al, 2011; Nardicchi et al, 2014).…”

Excitotoxicity, neuroinflammation and oxidant stress as molecular bases of epileptogenesis and epilepsy-derived neurodegeneration: The role of vitamin E

“…Worth of investigation could be the role of this vitamin as phospholipase inhibitor [128] that may eventually impact on the phospholipid (PL) metabolism of the neuronal membrane during spine formation. Other hypotheses include the protection of unsaturated lipids on phospholipid structures (further discussed later) that may preserve membrane integrity thus preventing degenerative (free radical-mediated) events and the activation of lipid turnover and eventually membrane demolition processes at spine site by the activity of specific phospholipase isoenzymes [138].…”

Rat Group IIA Secreted Phospholipase A2 Binds to Cytochrome c Oxidase and Inhibits Its Activity: A Possible Episode in the Development of Alzheimer’s Disease

“…However, in the context of our research, the most relevant is its association with the aetiology of neurodegenerative diseases. This enzyme is involved in the regulation of neurotransmission and neuritogenesis [ 5 ]. In connection with the latter, endogenous GIIA has been detected in mitochondria [ 6 ], but its function in this organelle remains speculative.…”