Characterization of inhibition by chronic treatment with lithium ion on nerve growth factor-induced neuronal differentiation of rat PC12 pheochromocytoma cells.
To understand the mechanism underlying the neurotoxicity of lithium ion, we investigated the inhibition of the nerve growth factor-induced neuronal differentiation of rat PC12 pheochromocytoma cells induced by treatment with LiCl. Incubation with 0.1-3 mM LiCl from 30 min before nerve growth factor (NGF) treatment attenuated neurite outgrowth. Moreover, incubation with 3 mM LiCl from 24 h before strongly reduced the neurite out-growth. The chronic pretreatment inhibited the NGF-caused induction of acetyl-cholinesterase activity known to be elevated by NGF in transcription-dependent processes, and inhibited expression of c-fos proto-oncogene mRNA. This pretreatment also inhibited the NGF-induced formation of inositol phosphates, accompanied by the significant accumulation of inositol monophosphate. These observations, that chronic treatment with LiCl inhibits the NGF-induced neuronal differentiation in a transcription-dependent manner and inhibits phosphoinositide metabolism, suggest a possible causal relationship between these two events.
Harada
H
H
Department of Environmental Biochemistry and Toxicology, School of Pharmaceutical Science, University of Shizuoka, Japan.
Sugiyama
T
T
Suketa
Y
Y
D000110:Acetylcholinesterase / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000378:metabolism; D008094:Lithium / Q000633:toxicity*; D009414:Nerve Growth Factors / Q000494:pharmacology*; D016501:Neurites / Q000187:drug effects; D016716:PC12 Cells / Q000187:drug effects* / Q000378:metabolism; D016760:Proto-Oncogene Proteins c-fos / Q000187:drug effects / Q000378:metabolism; D012333:RNA, Messenger / Q000187:drug effects; D051381:Rats
D007295:Inositol Phosphates; D009414:Nerve Growth Factors; D016760:Proto-Oncogene Proteins c-fos; D012333:RNA, Messenger; D008094:Lithium; D000110:Acetylcholinesterase