Regulation of pyruvate dehydrogenase activity in rat fat pads and isolated hepatocytes by levamisole.
The effect of levamisole on the catalytic activity of the pyruvate dehydrogenase (PDH) complex in rat adipose tissue segments and isolated hepatocytes was studied. Levamisole, an anthelmintic and immunotherapeutic agent with concentration-dependent oxidant/antioxidant properties, increased the catalytic activity of the pyruvate dehydrogenase complex in these systems. The activity of this enzyme complex may be regulated in part by protein-thiol modification. The treatment of rat adipose tissue segments and isolated hepatocytes with and without levamisole (0.1-3.0 mM) for 30 min resulted in a reversible increase in the catalytic activity of this enzyme complex. Levamisole at 1.5 mM and 2.0 mM were as potent as insulin (1.0 mU/ml) in adipose tissue and as dichloroacetate (2.0 mM) in isolated hepatocytes, respectively, in increasing the catalytic activity of the PDH complex. The stimulatory effects seen with levamisole were not accompanied by decreases in adenosine triphosphate (ATP) levels. The results of the present investigation suggest that the pyruvate dehydrogenase complex in adipose tissue and liver may be useful models for studying the mechanism of action of levamisole.
Thomaskutty
K G
KG
Department of Biochemistry and Molecular Biology, Howard University College of Medicine, Washington, DC 20059.
Basi
N S
NS
McKenzie
M L
ML
Pointer
R H
RH
D000273:Adipose Tissue / Q000187:drug effects* / Q000201:enzymology*; D000818:Animals; D002478:Cells, Cultured; D003999:Dichloroacetic Acid / Q000494:pharmacology; D004822:Epididymis / Q000187:drug effects / Q000201:enzymology; D007328:Insulin / Q000494:pharmacology; D007978:Levamisole / Q000494:pharmacology*; D008099:Liver / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D008297:Male; D011768:Pyruvate Dehydrogenase Complex / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D007328:Insulin; D011768:Pyruvate Dehydrogenase Complex; D007978:Levamisole; D003999:Dichloroacetic Acid