Carbofuran induces apoptosis of rat cortical neurons and down-regulates surface alpha7 subunit of acetylcholine receptors.
Carbofuran (CF), an anticholinesterase carbamate, is one of the most widely used N-methylcarbamate esters in insect and nematode control. Despite its serious adverse health effects on wildlife and humans, cellular and molecular studies of the damage of CF to CNS neurons are very limited. We have examined the cytotoxic effects of CF on cultured rat cortical cells, and the expression of the alpha7 subunit of the nicotinic acetylcholine receptor (alpha7 nAChR) in hippocampal neurons. CF was cytotoxic with an IC50 approximately 730 and approximately 640 microm when assessed by the lactate dehydrogenase (LDH) assay and propidium iodide (PI) staining, respectively, 3 days after treatment. CF induced DNA fragmentation and exposure of phosphatidyl serine (PS) on the cell surface. Surface labeling of the alpha7 nAChR with Alexa Fluor 488-conjugated alpha-bungarotoxin (alphaBgt) revealed a significant decrease in the density of the subunits in treated (500 microm CF) hippocampal neurons. Our data indicate that CF induces neuronal death by apoptosis and down-regulates nAChRs.
Kim
Sung Jin
SJ
Department of Anatomy and Medical Institute of Dongguk University, College of Medicine, Dongguk University, Gyeongju 780-714, Korea.
Kim
Jang Eok
JE
Ko
Bok Hyun
BH
Moon
Il Soo
IS
D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002235:Carbofuran / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000494:pharmacology*; D053938:DNA Fragmentation; D015536:Down-Regulation; D005260:Female; D005333:Fetus / Q000033:anatomy & histology; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism; D006801:Humans; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D011247:Pregnancy; D021122:Protein Subunits / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D064569:alpha7 Nicotinic Acetylcholine Receptor
D017304:Annexin A5; D002800:Cholinesterase Inhibitors; C579167:Chrna7 protein, human; C579165:Chrna7 protein, rat; D021122:Protein Subunits; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor; D002235:Carbofuran