Regeneration of acetylcholinesterase in clonal neuroblastoma-glioma hybrid NG108-15 cells after soman inhibition: effect of glycyl-L-glutamine.
Acetylcholinesterase (AChE) in the clonal NG108-15 cell line has been previously characterized. This cell line represents an in vitro system to study AChE regulation and effects of chemical compounds that may alter AChE activity. Recently, glycyl-L-glutamine (GLG) was demonstrated to function as a neurotrophic factor for maintenance of AChE content in cat denervated superior cervical ganglion cells. In the present study, regeneration of AChE activity in cultures of undifferentiated NG108-15 cells after soman inhibition was investigated in the presence and absence of GLG. Cells were treated with soman (5.5 x 10(-6) M) for 15 min and then washed to remove excess soman. Culture medium containing either GLG (10(-6), 10(-5), or 10(-4) M) or glycyl-L-glutamic acid (10(-6) M) was added to cultures after soman treatment and remained in the medium until cell harvest. Cells were physically detached at various times after soman treatment and specific AChE activity was determined. After soman, AChE activity dramatically decreased to less than 1% of untreated cellular activity at 1 hr. AChE activity gradually increased after 5 hr, while untreated cell AChE activity was regained 20 hr after soman. The t1/2 for AChE regeneration was approximately 10 hr. GLG did not increase the rate of AChE regeneration after soman inhibition. These results indicate that GLG is not a directly acting neurotrophic factor for AChE synthesis in NG108-15 cells after chemical AChE inactivation.
Applied Pharmacology Branch, U.S. Army Medical Research Institute of Chemical Defense Aberdeen Proving Ground, Maryland 21010-5425.
J J
JJ
Yourick
P A
PA
Eklo
M P
MP
McCluskey
R
R
Ray
D000110:Acetylcholinesterase / Q000378:metabolism*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004151:Dipeptides / Q000494:pharmacology*; D005910:Glioma / Q000201:enzymology; D051379:Mice; D009447:Neuroblastoma / Q000201:enzymology; D012999:Soman / Q000633:toxicity*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000201:enzymology
D002800:Cholinesterase Inhibitors; D004151:Dipeptides; C039788:glycylglutamine; D012999:Soman; D000110:Acetylcholinesterase