Biochemical changes in primary culture of skeletal muscle cells following dimethoate exposure.
In order to investigate the cellular mechanism of muscular weakness in the Intermediate Myasthenia Syndrome (IMS) following acute organophosphate poisoning, we studied the cytotoxicity of dimethoate and its effects on the activity of acetylcholine esterase (AChE), Na+-K+-ATPase, succinate dehydrogenase (SDH), and Ca2+-ATPase in primary cultured skeletal muscle cells. The results showed that the activity of AChE was significantly inhibited in a dose and time-dependent manner when cells were exposed to dimethoate for 2 h, but the expression of heat-shock protein (HSP70) in muscle cells was significantly increased in a time-dependent manner following dimethoate exposure. Dimethoate can significantly increase the activity of Na+-K+-ATPase in the mitochondrial and cytoplasm fraction of muscle cells, and inhibit the activity of Ca2+-ATPase. This study suggests that the disruption of intracellular homeostasis and energy metabolism of the muscle cells may play a role in the etiology of IMS.
Yang
Dongren
D
Center for Research on Occupational and Environmental Toxicology, L606, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Road, Portland 97201-3098, USA. yangdo@ohsu.edu
Lu
Xinfang
X
Zhang
Weiguo
W
He
Fengsheng
F
D000110:Acetylcholinesterase / Q000097:blood; D000818:Animals; D015153:Blotting, Western; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002800:Cholinesterase Inhibitors / Q000633:toxicity*; D004117:Dimethoate / Q000633:toxicity*; D004354:Drug Screening Assays, Antitumor; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007306:Insecticides / Q000633:toxicity*; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013385:Succinate Dehydrogenase / Q000378:metabolism
D002800:Cholinesterase Inhibitors; D018840:HSP70 Heat-Shock Proteins; D007306:Insecticides; D013385:Succinate Dehydrogenase; D000110:Acetylcholinesterase; D000252:Calcium-Transporting ATPases; D000254:Sodium-Potassium-Exchanging ATPase; D004117:Dimethoate