Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0017638 (
glioma
)
30,880
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
The toxic effects of physostigmine, an anticholinesterase drug, and its metabolite eseroline were investigated in three neuronal cell culture systems, mouse neuroblastoma N1E-115, rat
glioma
C6, and neuroblastoma-
glioma
hybrid NG 108-15. Physostigmine and eseroline (0.5 nM) elicited a time-dependent leakage of
lactic acid dehydrogenase
(
LDH
) from all three cell types. An increased release of [14C]adenine nucleotides was also detected from cells when they were prelabeled with [14C]adenine. Eseroline was comparatively more toxic than the parent compound, physostigmine. Eseroline elicited a dose- and time-dependent leakage of
LDH
and release of adenine nucleotides from the neuronal cells. A nonneuronal cell line, rat liver ARL-15, was comparatively the most resistant cell type to eseroline toxicity. The concentrations of eseroline needed for 50% release of adenine nucleotides or 50% leakage of
LDH
from NG-108-15 and N1E-115 cells in 24 hr ranged from 40 to 75 microM. The concentrations of eseroline needed to obtain similar responses in C6 and ARL-15 cells were much higher and ranged from 80 to 120 microM. Phase contrast microscopy showed extensive damage to three neuronal cell lines at concentrations of eseroline as low as 75 microM. The loss of ATP from N1E-115 cells exceeded 50% when they were treated with 0.3 mM eseroline for 1 hr--at which time the leakage of
LDH
was not detectable. It seems that eseroline causes neuronal cell death by a mechanism involving loss of cell ATP. Thus, the formation of eseroline may contribute to the toxic effect of physostigmine.
...
PMID:Eseroline, a metabolite of physostigmine, induces neuronal cell death. 225 81
