title: Polyphosphoinositide metabolism and Golgi complex morphology in hippocampal neurons in primary culture is altered by chronic ethanol exposure.
abstract: OBJECTIVE
  Ethanol affects not only the cytoskeletal organization and activity, but also intracellular trafficking in neurons in the primary culture. Polyphosphoinositide (PPIn) are essential regulators of many important cell functions, including those mentioned, cytoskeleton integrity and intracellular vesicle trafficking. Since information about the effect of chronic ethanol exposure on PPIn metabolism in neurons is scarce, this study analysed the effect of this treatment on three of these phospholipids.
  
  
  METHODS
  Phosphatidylinositol (PtdIns) levels as well as the activity and/or levels of enzymes involved in their metabolism were analysed in neurons chronically exposed to ethanol. The levels of phospholipases C and D, and phosphatidylethanol formation were also assessed. The consequence of the possible alterations in the levels of PtdIns on the Golgi complex (GC) was also analysed.
  
  
  RESULTS
  We show that phosphatidylinositol (4,5)-bisphosphate and phosphatidylinositol (3,4,5)-trisphosphate levels, both involved in the control of intracellular trafficking and cytoskeleton organization, decrease in ethanol-exposed hippocampal neurons. In contrast, several kinases that participate in the metabolism of these phospholipids, and the level and/or activity of phospholipases C and D, increase in cells after ethanol exposure. Ethanol also promotes phosphatidylethanol formation in neurons, which can result in the suppression of phosphatidic acid synthesis and, therefore, in PPIn biosynthesis. This treatment also lowers the phosphatidylinositol 4-phosphate levels, the main PPIn in the GC, with alterations in their morphology and in the levels of some of the proteins involved in structure maintenance.
  
  
  CONCLUSIONS
  The deregulation of the metabolism of PtdIns may underlie the ethanol-induced alterations on different neuronal processes, including intracellular trafficking and cytoskeletal integrity.
authors.affiliation: Corresponding author: Sección de Biología y Patología Celular, Centro de Investigación, Hospital Universitario La Fe, Avda. Campanar 21, Valencia, Spain. renau_jai@gva.es
authors.forename: Guillermo
authors.initials: G
authors.lastname: Esteban-Pretel
authors.forename: María Pilar
authors.initials: MP
authors.lastname: Marín
authors.forename: Ana María
authors.initials: AM
authors.lastname: Romero
authors.forename: Joaquín
authors.initials: J
authors.lastname: Timoneda
authors.forename: Xavier
authors.initials: X
authors.lastname: Ponsoda
authors.forename: Raúl
authors.initials: R
authors.lastname: Ballestín
authors.forename: Jaime
authors.initials: J
authors.lastname: Renau-Piqueras
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D005260:Female; D006056:Golgi Apparatus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D018129:Phosphatidylinositol Phosphates; D000431:Ethanol