PMID- 10978589 OWN - NLM STAT- MEDLINE DCOM- 20001017 LR - 20191210 IS - 0304-3940 (Print) IS - 0304-3940 (Linking) VI - 291 IP - 2 DP - 2000 Sep 15 TI - Neurotrophic factor protection against ethanol toxicity in rat cerebellar granule cell cultures requires phosphatidylinositol 3-kinase activation. PG - 121-5 AB - 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. FAU - Heaton, M B AU - Heaton MB AD - University of Florida Brain Institute, Department of Neuroscience, Centre for Alcohol Research, Box 100244, FL, 32610-0244, Gainesville, USA. heaton.ufbi.ufl.edu FAU - Kim, D S AU - Kim DS FAU - Paiva, M AU - Paiva M LA - eng GR - AA09128/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, P.H.S. PL - Ireland TA - Neurosci Lett JT - Neuroscience letters JID - 7600130 RN - 0 (Androstadienes) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Neuroprotective Agents) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 3K9958V90M (Ethanol) RN - 9061-61-4 (Nerve Growth Factor) RN - XVA4O219QW (Wortmannin) SB - IM MH - Androstadienes/pharmacology MH - Animals MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cells, Cultured MH - Cerebellum/cytology/*drug effects/*enzymology MH - Cytoplasmic Granules/drug effects/enzymology MH - Enzyme Activation/drug effects MH - Ethanol/*antagonists & inhibitors/*toxicity MH - Male MH - Nerve Growth Factor/metabolism MH - Neuroprotective Agents/*pharmacology MH - Phosphatidylinositol 3-Kinases/*metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Rats MH - Rats, Long-Evans MH - Wortmannin EDAT- 2000/09/09 11:00 MHDA- 2000/10/21 11:01 CRDT- 2000/09/09 11:00 PHST- 2000/09/09 11:00 [pubmed] PHST- 2000/10/21 11:01 [medline] PHST- 2000/09/09 11:00 [entrez] AID - S0304-3940(00)01398-7 [pii] AID - 10.1016/s0304-3940(00)01398-7 [doi] PST - ppublish SO - Neurosci Lett. 2000 Sep 15;291(2):121-5. doi: 10.1016/s0304-3940(00)01398-7.