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

    Recent studies have focused on three major groups of PLA: the group IV calciumdependent cytosolic PLA. PLA cPLA cPLA belongs to the group IV PLA s.Recent studies have provided evidence for translocation of cPLA from the cytosol to nuclear membranes. In macrophages, as well as in other cell systems, agents including G proteincoupled receptor agonists, calcium ionophores, phorbol esters, and zymogens can activate cPLA, resulting in AA release. . A scheme representing different PLA pathways in astrocytes and neurons.The group II sPLA s, including IIA, IIC, IID, IIE, and IIF isoforms, are lowmolecularweight proteins with secretory sequences.Genes for many of the group II sPLA isoforms are clustered in chromosome. Of the group II sPLA s, the IIA enzyme has been studied extensively because of its involvement in inammatory processes in the peripheral systems. In the CNS, group IIA sPLA mRNA is expressed in cultured astrocytes and can be induced in response to proinammatory cytokines. Group VIA enzyme has at least ve splice variants, all with ankyrin repeats, whereas group VIB iPLA lacks ankyrin repeats but consists of a signal motif for peroxisome localization. Astrocytes have been shown to contain all major groups of PLA. Therefore, these cells have been used to study the roles of different groups of PLA in normal physiological and pathological functions.One reason for this interest is that in the brain, ATP is stored at high concentrations in synaptic vesicles and is coreleased with neurotransmitters during neuronal excitation. Therefore, PY receptors in astrocytes may constitute an important mechanism for mediating communication between neurons and glial cells.In astrocytes, activation of PY receptors is implicated in reactive gliosis, a pathological condition associated with a number of neurodegenerative diseases. Several studies have demonstrated the ability of ATP UTP to stimulate AA release in astrocytes further demonstrated the role of the extracellular signalregulated protein kinase pathways for enhancing cPLA phosphorylation and stimulating AA release in murine astrocytes.ATP, acting on the PY receptors in astrocytes, could also mediate the release of docosahexaenoic acid. These results indicate the ability of ATP to stimulate multiple pathways that lead to activation of different PLA isoforms.The activation of endothelin receptor, another G proteincoupled receptor, was shown to cause AA release in astrocytes. The study with smooth muscle cells further demonstrated the involvement of PKC and p MAP kinase in endothelinmediated AA release. Increases in both iand PKC are important factors in the translocation and phosphor ylation of cPLA.These results illustrate the complexity of different intracellular Targetmol’s Bromhexine hydrochloride signaling pathways in the regulation of cPLA.Excessive generation of ROS in the CNS has been implicated in neuronal damage resulting from cerebral ischemia and in AD.Oxidant compounds such as HO have been shown to cause perturbation of cell membrane integrity and alteration of mitochondrial function, resulting in an increase in i. In fact, HO is a naturally occurring oxidant produced by a number of intracellular reactions, and excessive production of this compound is associated with signaling pathways. In astrocytes, HO can alter phospholipidhydrolyzing enzymes, including phospholipase D. A study in murine astrocytes further indicated the involvement of cPLA and iPLA in AA release induced by HO.