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  • Whitley Vistisen posted an update 3 months, 2 weeks ago

    In another study in rat astrocytes, LPS also increased Targetmol’s Omadacycline expression of sPLA mRNA but not cPLA mRNA. Although cytokines did not increase cPLA mRNA levels, an increase in cPLA phosphorylation was observed further indicated the role of sPLA in cytokineinduced production of PGE.Taken together, these results suggest the involvement of both sPLA and cPLA in cytokinemediated PGE production.Results from the above studies suggest that in pathological conditions associated with an increase in inammation, a sustained increase in proinammatory cytokines in the brain may enhance the response of G proteincoupled receptors to produce higher levels of eicosanoids.In a recent study in our laboratory, exposure of murine astrocytes to L for hresulted in an increase in COX and cPLA immunoreactivity. In addition to group IIA sPLA, group V sPLA was also present in astrocytes, and TNF stimulated both types of sPLA, albeit through different time courses and different pathways. These studies demonstrate that different cytokines can activate different isoforms of sPLA in astrocytes.This is due in part to difculties in isolating sufcient quantities of these cells for biochemical analysis.Microglial cells are immuneactive cells and exhibit many properties similar to those of macrophages and astrocytes. Therefore, there is substantial interest in the role of PLA in the inammatory responses in these cells.Although the murinederived BV microglial cells lack the group IIA sPLA, they contain high levels of cPLA. Astrocytes were plated on coverslips coated with poly dlysine and grown to conuence.Immediately after treatment, cells were xed with paraformaldehyde in phosphatebuffered saline at C for min.Incubation with secondaryantibodies was carried out at C for h.The stained cells were viewed with a confocal microscope. In human microglial cells, LPS was capable of inducing COX mRNA expression and PGE production. These results suggest that PLA may also play a role in mediating the inammatory cascade in microglial cells.PLA IN NEURONS AA is regarded as a neuromodulator in the CNS, and PLA is thought to have a role in neuronal plasticity and stimulation with excitatory neurotransmitter agonists such as aminohydroxymethylisoxazole propionic acid, as well as muscarinic cholinergic agonists, can stimulate AA release in neurons.Furthermore, oxidant compounds such as HO could further enhance AA release stimulated by a number of neurotransmitter agonists. Studies in vivo have demonstrated cPLA mRNA expression in hippocampal neurons. Infusion of NMDA into the hippocampus resulted in the activation of cPLA and COX expression and the production of PGE and PGF. In human neuroblastoma LAN cells, an isoform of iPLA was shown to specically utilize phosphatidylethanolamine. Differentiation of these cells with retinoic acid was marked by an increase in iPLA activity in the nuclei, suggesting a role for this PLA in regulating nuclear membrane functions. In another human neuroblastoma cell line, SKNSH, iPLA was involved in IL stimulation of COX expression and PGE secretion. Therefore, studies with neuroblastoma cells have revealed novel functions of iPLA.In this review, an attempt was made to cover studies on PLA in cerebral ischemia, AD, and neurodegeneration due to excitotoxic compounds.Many of these changes are associated with an increase in oxidative stress, resulting in the production of ROS, which in turn, are important factors underlying delayed neuron cell death.