Species differences in the intracellular distribution of ciprofibroyl-CoA hydrolase. Implications for peroxisome proliferation.
Peroxisomal proliferators (HPP), such as ciprofibrate and clofibric acid, are species-specific drugs. Since HPP-coenzyme A derivatives might be involved in their action, we studied the subcellular distribution of liver ciprofibroyl-CoA hydrolase in rat and in two HPP-unresponsive species, humans and guinea pig. Total activity was similar in the three species and was not induced by clofibric acid treatment. In guinea pig, as in humans, the enzyme is localized in the mitochondrial and soluble fractions and no changes are observed after drug treatment. In the rat, the enzyme has a microsomal localization, but upon clofibric acid treatment it changes to a mitochondrial and soluble distribution, as in unresponsive species. These results raise the possibility that drug-induced hydrolases in rats might be normally expressed in humans and guinea pigs.
Urrea
R
R
Departamento de Biológia Celular y Molecular, Facultad de Ciencias Biologicas, P. Universidad Catolica de Chile, Santiago.
Bronfman
M
M
D000818:Animals; D002995:Clofibric Acid / Q000494:pharmacology; D003066:Coenzyme A Ligases / Q000187:drug effects / Q000378:metabolism*; D006168:Guinea Pigs; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000648:ultrastructure; D008830:Microbodies / Q000187:drug effects / Q000201:enzymology*; D008861:Microsomes / Q000737:chemistry / Q000201:enzymology; D008930:Mitochondria, Liver / Q000187:drug effects / Q000201:enzymology; D010170:Palmitoyl-CoA Hydrolase / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D013045:Species Specificity; D013347:Subcellular Fractions; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D002995:Clofibric Acid; D010170:Palmitoyl-CoA Hydrolase; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase