PMID- 9648866
OWN - NLM
STAT- MEDLINE
DCOM- 19980709
LR  - 20190630
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 71
IP  - 1
DP  - 1998 Jul
TI  - Ethanol induces apoptosis in cerebellar granule neurons by inhibiting 
      insulin-like growth factor 1 signaling.
PG  - 196-204
AB  - The ability of ethanol to interfere with insulin-like growth factor 1 
      (IGF-1)-mediated cell survival was examined in primary cultured cerebellar 
      granule neurons. Cells underwent apoptosis when switched from medium containing 
      25 mM K+ to one containing 5 mM K+. IGF-1 protected granule neurons from 
      apoptosis in medium containing 5 mM K+. Ethanol inhibited IGF-1-mediated neuronal 
      survival but did not inhibit IGF-1 receptor binding or the neurotrophic action of 
      elevated K+, and failed to potentiate cell death in the presence of 5 mM K+. 
      Inhibition of neuronal survival by ethanol was not reversed by increasing the 
      concentration of IGF-1. Significant inhibition by ethanol (15-20%) was observed 
      at 1 mM and was half-maximal at 45 mM. The inhibition of IGF-1 protection by 
      ethanol corresponded to a marked reduction in the phosphorylation of insulin 
      receptor substrate 1, the binding of phosphatidylinositol 3-kinase (PI 3-kinase), 
      and a block of IGF-1-stimulated PI 3-kinase activity. The neurotrophic response 
      of IGF-1 was also inhibited by the PI 3-kinase inhibitor LY294002, the protein 
      kinase C inhibitor chelerythrine chloride, and the protein kinase A inhibitor 
      KT5720, but unaffected by the mitogen-activated protein kinase kinase inhibitor 
      PD 98059. These data demonstrate that ethanol promotes cell death in cerebellar 
      granule neurons by inhibiting the antiapoptotic action of IGF-1.
FAU - Zhang, F X
AU  - Zhang FX
AD  - Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, 
      Philadelphia, Pennsylvania 19107, USA.
FAU - Rubin, R
AU  - Rubin R
FAU - Rooney, T A
AU  - Rooney TA
LA  - eng
GR  - AA09976/AA/NIAAA NIH HHS/United States
GR  - AA10413/AA/NIAAA NIH HHS/United States
GR  - K02 AA123/AA/NIAAA NIH HHS/United States
GR  - etc.
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (Central Nervous System Depressants)
RN  - 3K9958V90M (Ethanol)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Receptor, IGF Type 1)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Central Nervous System Depressants/*pharmacology
MH  - Cerebellum/cytology
MH  - Dose-Response Relationship, Drug
MH  - Ethanol/*pharmacology
MH  - Insulin-Like Growth Factor I/*metabolism
MH  - Neurons/chemistry/*cytology/enzymology
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, IGF Type 1/agonists/metabolism
MH  - Signal Transduction/*drug effects
EDAT- 1998/07/02 00:00
MHDA- 1998/07/02 00:01
CRDT- 1998/07/02 00:00
PHST- 1998/07/02 00:00 [pubmed]
PHST- 1998/07/02 00:01 [medline]
PHST- 1998/07/02 00:00 [entrez]
AID - 10.1046/j.1471-4159.1998.71010196.x [doi]
PST - ppublish
SO  - J Neurochem. 1998 Jul;71(1):196-204. doi: 10.1046/j.1471-4159.1998.71010196.x.