title: Effect of aniracetam on phosphatidylinositol transfer protein alpha in cytosolic and plasma membrane fractions of astrocytes subjected to simulated ischemia in vitro.
abstract: Brain ischemia affects phosphoinositide metabolism and the level of lipid-derived second messengers. Phosphatidylinositol transfer proteins (PI-PTs) are responsible for the transport of phosphatidylinositol (PI) and other phospholipids through membranes. Isoform of PI-TPs (PI-TPalpha) is an essential component in ensuring substrate supply for phospholipase C (PLC). The current study was conducted to examine potential effect of aniracetam on PI-TPalpha expression and to characterize the PI-TPalpha isoform distribution between membrane and cytosol fractions of astrocytes exposed to simulated ischemia in vitro. After 8 h period of ischemia, the level of PI-TPalpha was significantly higher in cytosol (by about 28%) as well as in membrane fraction (by about 80%) in comparison with control. We have found that aniracetam treatment of astrocytes in normoxia significantly increased the level of PI-TPalpha in membrane fraction with a maximal effect at 0.1 microM concentration of aniracetam (by about 195% of control). In membrane fractions of ischemic cells, aniracetam increased PI-TPalpha expression in a concentration-dependent manner. In ischemic cells, aniracetam (10 microM) has elevated PI-TPalpha expression up to 155% and 428% in cytosolic and membrane fractions in comparison with ischemic untreated cells, respectively. The study has shown that aniracetam significantly activates PI-TPalpha in cell membrane fraction and this effect might be connected with previously described activation of MAP kinase cascade.
authors.affiliation: Department of Pharmacology, Silesian Medical University, Medykó 18, PL 40-752 Katowice, Poland. bgabryel@interia.pl
authors.forename: Bozena
authors.initials: B
authors.lastname: Gabryel
authors.forename: Małgorzata
authors.initials: M
authors.lastname: Chalimoniuk
authors.forename: Andrzej
authors.initials: A
authors.lastname: Małecki
authors.forename: Joanna  B
authors.initials: J
authors.lastname: Strosznajder
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D015153:Blotting, Western; D002545:Brain Ischemia / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism*; D004591:Electrophoresis, Polyacrylamide Gel; D018697:Nootropic Agents / Q000494:pharmacology*; D049294:Phospholipid Transfer Proteins / Q000096:biosynthesis*; D011760:Pyrrolidinones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D018697:Nootropic Agents; D049294:Phospholipid Transfer Proteins; D011760:Pyrrolidinones; C036466:aniracetam