2,3,7,8-Tetrachlorodibenzo-p-dioxin induced alterations of pyruvate carboxylase levels and lactate dehydrogenase isozyme shifts in C57BL/6J male mice.
A dose-dependent reduction of hepatic pyruvate carboxylase levels and activity occurs in C57BL/6J male mice given 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) i.p. in a corn oil carrier. The dose range was from 1 to 75 micrograms/kg body weight and the analysis was done 8 days postinjection. At the maximum TCDD level investigated, we found a 10-fold reduction in pyruvate carboxylase activity. Furthermore, TCDD at a dose of 1 microgram/kg body weight blocks corn oil induction of an increase in the amount of pyruvate carboxylase in liver protein extracts. At doses beyond those required to initiate a reduction in pyruvate carboxylase, lactate dehydrogenase isozyme patterns shift. This is accompanied by an increase in blood lactic acid levels. We propose that TCDD-mediated reduction in pyruvate carboxylase and lactate dehydrogenase isozyme shifts may represent a major component in TCDD toxicity.
Sparrow
B R
BR
Department of Biochemistry and Biophysics, Oregon State University, Corvallis 97331.
Thompson
C S
CS
Ryu
B W
BW
Selevonchick
D P
DP
Schaup
H W
HW
D000818:Animals; D015153:Blotting, Western; D004591:Electrophoresis, Polyacrylamide Gel; D007527:Isoenzymes; D007770:L-Lactate Dehydrogenase / Q000378:metabolism*; D007773:Lactates / Q000097:blood; D019344:Lactic Acid; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology*; D011766:Pyruvate Carboxylase / Q000378:metabolism*
D007527:Isoenzymes; D007773:Lactates; D000072317:Polychlorinated Dibenzodioxins; D019344:Lactic Acid; D007770:L-Lactate Dehydrogenase; D011766:Pyruvate Carboxylase