Neurotrophic factor protection against ethanol toxicity in rat cerebellar granule cell cultures requires phosphatidylinositol 3-kinase activation.
Neonatal rat cerebellar granule cells were used to assess the possible role of the phosphatidylinositol 3-kinase (PI3-K) signaling pathway in the neuroprotective effects of neurotrophic factors against ethanol toxicity. Culture conditions included medium with ethanol (400 and 600 mg/dl), nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF), ethanol+NGF or BDNF, the PI3-K inhibitor wortmannin (10 or 100 microM), and wortmannin+ethanol+NGF or BDNF. Neuronal survival was determined via the MTT assay. The results indicated that both NGF and BDNF ameliorate ethanol neurotoxicity, and wortmannin abolished this effect, except at the higher ethanol concentration combined with the lower wortmannin level. These data strongly implicate the PI3-K pathway in growth factor protection against ethanol neurotoxicity.
Heaton
M B
MB
University of Florida Brain Institute, Department of Neuroscience, Centre for Alcohol Research, Box 100244, FL, 32610-0244, Gainesville, USA. heaton.ufbi.ufl.edu
Kim
D S
DS
Paiva
M
M
D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D000431:Ethanol / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D008297:Male; D020932:Nerve Growth Factor / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D020318:Rats, Long-Evans; D000077191:Wortmannin
D000730:Androstadienes; D019208:Brain-Derived Neurotrophic Factor; D000431:Ethanol; D020932:Nerve Growth Factor; D018696:Neuroprotective Agents; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D000077191:Wortmannin