Hepatic peroxisome proliferation in vitamin A-deficient mice without a simultaneous increase in peroxisomal acyl-CoA oxidase activity.
Vitamin A-adequate and vitamin A-deficient C57B1/6 mice were treated for ten days with 0.02% (w/w) perfluorooctanoic acid (PFOA) in their diet. Treated vitamin A- adequate and -deficient mice demonstrated approximately the same increases in liver somatic index (g liver/g body weight) (somewhat more than 2-fold) and mitochondrial protein content (5-fold). PFOA treatment resulted in a 26-fold increase in hepatic peroxisomal lauroyl-CoA oxidase activity in vitamin A-adequate mice, whereas the same activity was unchanged in vitamin A-deficient mice. Vitamin deficiency itself caused a 3- to 4- fold increase in cytosolic catalase activity and a smaller increase in the activity of microsomal cytochrome P-450 IVA (lauric acid omega- and omega-1 hydroxylase) in this same organ. The induction of the activities of these enzymes was less prominent in vitamin A-deficient mice compared with the effect caused by PFOA in vitamin A-adequate mice, resulting in approximately the same maximal values for these parameters in both groups (i.e approx 21 micromol/g liver - min and 350 nanomol/g liver - min, respectively). A 70 kDa protein, presumable the multifunction protein, was shown by Commassie blue staining of SDS-polyacrylamide gels and by immunoblotting (with antibodies towards the multifunctional protein) to be induced to approximately the same degree in vitamin A-adequate and deficient mice. A morphometric study revealed that PFOA causes the same extent of hepatic peroxisome proliferation in vitamin A-deficient as in vitamin A-adequate mice. The possibility that PFOA exerts its effect in vivo through at least two different mechanisms is discussed.
Sohlenius
A K
AK
Department of Biochemistry, Wallenberg Laboratory, Stockholm University, Sweden.
Reinfeldt
M
M
Bäckström
K
K
Bergstrand
A
A
DePierre
J W
JW
D042962:Acyl-CoA Oxidase; D000818:Animals; D002210:Caprylates / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D042926:Cytochrome P-450 CYP4A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D003600:Cytosol / Q000201:enzymology; D004790:Enzyme Induction; D005466:Fluorocarbons / Q000494:pharmacology; D008099:Liver / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008830:Microbodies / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000378:metabolism; D010088:Oxidoreductases / Q000378:metabolism*; D010170:Palmitoyl-CoA Hydrolase / Q000378:metabolism; D014801:Vitamin A / Q000378:metabolism; D014802:Vitamin A Deficiency / Q000201:enzymology / Q000378:metabolism*
D002210:Caprylates; D005466:Fluorocarbons; D014801:Vitamin A; D003577:Cytochrome P-450 Enzyme System; C023036:perfluorooctanoic acid; D006899:Mixed Function Oxygenases; D010088:Oxidoreductases; D002374:Catalase; D042926:Cytochrome P-450 CYP4A; D042962:Acyl-CoA Oxidase; D010170:Palmitoyl-CoA Hydrolase