Ethanol perturbs the secretory pathway in astrocytes.
Ethanol exposure induces retention of glycoproteins in growing astrocytes. We examined the intracellular sites at which this retention occurs and investigated whether this effect is accompanied by alterations in the Golgi complex and microtubular system. We studied the effects of ethanol on the Golgi complex structure, as well as on the secretory pathway functionality by monitoring both the transport of the VSV-G protein and the protein levels of several molecules involved in the regulation of this pathway. Ethanol was found to delay VSV-G transport, modify Golgi complex morphology, and reduce the number of secretory vesicles. Moreover, ethanol affected the levels of mannosidase II, p58, betaCOP, rbet1, and several Rab GTPases. It also affected microtubule organization and polymerization and the levels of the motor proteins kinesin and dynein. Most of these effects were dose-dependent. These alterations, together with those previously reported concerning biosynthesis of glycoconjugates, provide novel insights into how ethanol impairs brain development.
Tomás
Mónica
M
Sección de Biología y Patología Celular, Centro de Investigación, Hospital Universitario La Fe, Av. Campanar 21, E-46009 Valencia, Spain.
Marín
Pilar
P
Megías
Luís
L
Egea
Gustavo
G
Renau-Piqueras
Jaime
J
D020268:Alcohol-Induced Disorders, Nervous System / Q000378:metabolism / Q000503:physiopathology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000254:growth & development* / Q000503:physiopathology; D002478:Cells, Cultured; D020756:Coatomer Protein / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000633:toxicity*; D005260:Female; D063647:Fetal Alcohol Spectrum Disorders / Q000378:metabolism / Q000503:physiopathology; D006056:Golgi Apparatus / Q000187:drug effects* / Q000378:metabolism; D037241:Mannose-Binding Lectins / Q000187:drug effects / Q000378:metabolism; D008361:Mannosidases / Q000187:drug effects / Q000378:metabolism; D008565:Membrane Proteins / Q000187:drug effects / Q000378:metabolism; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D020409:Molecular Motor Proteins / Q000187:drug effects / Q000378:metabolism; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism / Q000503:physiopathology; D050767:Qc-SNARE Proteins / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D022142:Secretory Vesicles / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D033921:Vesicular Transport Proteins / Q000187:drug effects / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000187:drug effects / Q000378:metabolism
C098783:BET1 protein, rat; D020756:Coatomer Protein; C084004:LMAN1 protein, human; D037241:Mannose-Binding Lectins; D008565:Membrane Proteins; D020409:Molecular Motor Proteins; D050767:Qc-SNARE Proteins; D033921:Vesicular Transport Proteins; D000431:Ethanol; D008361:Mannosidases; C038829:mannosyl-oligosaccharide 1,3 - 1,6-alpha-mannosidase; D020691:rab GTP-Binding Proteins