title: The differential regulation of group II(A) and group V low molecular weight phospholipases A(2) in cultured rat astrocytes.
abstract: In astrocytes, cytokines stimulate the release of secretory phospholipase A(2) (sPLA(2)) activity and group II(A) sPLA(2) expression. This paper reports that two sPLA(2) isoforms, group II(A) and group V, are in fact expressed by astrocytes. Our studies showed that tumor necrosis factor alpha (TNFalpha) enhanced the mRNA of both isoforms, but the time courses of enhancement differed; group V was induced much faster than group II(A). Moreover, TNFalpha stimulated both the NF-kappaB and mitogen-activated protein (MAP) kinase (extracellular signal-regulated kinase, c-Jun NH(2)-terminal kinase, and p38 MAP kinase) signaling pathways in astrocytes. Interestingly, PI 3-kinase activity also was enhanced by TNFalpha, and NF-kappaB pathway was involved in mediating its effect. Specific inhibitors were used to show that both extracellular signal-regulated kinase and p38 MAP kinase may contribute to the effect of TNFalpha and that blocking phosphatidylinositol 3-kinase activity fully reversed the effect of TNFalpha. Furthermore, in astrocytes, TNFalpha-induced release of sPLA(2) activity was partially reversed by thyroid hormone and almost abolished by growth factors. This phenomenon was accompanied by a less marked increase in both group II(A) and group V sPLA(2) mRNA. In the presence of growth factors, the increase in group V mRNA was inhibited early and transiently, in contrast to what was observed with group II(A), which was more persistently inhibited. Although a transcriptional effect of thyroid hormone or growth factors in astrocytes cannot be definitively excluded, both types of factor interfered with sPLA(2) expression in a manner suggesting the existence of regulation of post-transcriptional events.
authors.affiliation: INSERM, Unité de Recherches sur la Glande Thyroïde et la Régulation Hormonale, 94276 Le Kremlin-Bicêtre, France.
authors.forename: G
authors.initials: G
authors.lastname: Thomas
authors.forename: F
authors.initials: F
authors.lastname: Bertrand
authors.forename: B
authors.initials: B
authors.lastname: Saunier
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000201:enzymology*; D002478:Cells, Cultured; D019902:Chondrocytes / Q000201:enzymology; D004790:Enzyme Induction; D006133:Growth Substances / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D008970:Molecular Weight; D016328:NF-kappa B / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D013963:Thyroid Hormones / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D006133:Growth Substances; D007527:Isoenzymes; D016328:NF-kappa B; D012333:RNA, Messenger; D013963:Thyroid Hormones; D014409:Tumor Necrosis Factor-alpha; D019869:Phosphatidylinositol 3-Kinases; D020929:Mitogen-Activated Protein Kinase Kinases; D010741:Phospholipases A