Activity of peroxisomal enzymes, and levels of polyamines in LPA-transgenic mice on two different diets.
BACKGROUND
In man, elevated levels of plasma plipoprotein (a) (Lp(a)) is a cardiovascular risk factor, and oxidized phospholipids are believed to play a role as modulators of inflammatory processes such as atherosclerosis. Polyamines are potent antioxidants and anti-inflammatory agents. It was therefore of interest to examine polyamines and their metabolism in LPA transgenic mice. Concentration of the polyamines putrescine, spermidine and spermine as well as the activity of peroxisomal polyamine oxidase and two other peroxisomal enzymes, acyl-CoA oxidase and catalase were measured. The mice were fed either a standard diet or a diet high in fat and cholesterol (HFHC). Some of the mice in each feeding group were in addition given aminoguanidine (AG), a specific inhibitor of diamine oxidase, which catalyses degradation of putrescine, and also inhibits non-enzymatic glycosylation of protein which is implicated in the aetiology of atherosclerosis in diabetic patients. Non-transgenic mice were used as controls.


RESULTS
Intestinal peroxisomal polyamine oxidase activity was significantly higher in LPA transgenic mice than in the non-transgenic mice, while intestinal peroxisomal catalase activity was significantly lower. Hepatic beta-oxidation increased in Lp(a) transgenic mice fed the HFHC diet, but not in those on standard diet. Hepatic spermidine concentration was increased in all mice fed the HFHC diet compared to those fed a standard diet, while spermine concentration was decreased. With exception of the group fed only standard diet, transgenic mice showed a lower degree of hepatic steatosis than non-transgenic mice. AG had no significant effect on hepatic steatosis.


CONCLUSIONS
The present results indicate a connection between peroxisomal enzyme activity and the presence of the human LPA gene in the murine genome. The effect may be a result of changes in oxidative processes in lipid metabolism rather than resulting from a direct effect of the LPA construct on the peroximal gene expression.
Eliassen
Knut A
KA
Department Basic Sciences and Aquatic Medicine, Norwegian School of Veterinary Science, PO Box 8146, Dep. No-0033 Oslo, Norway. knut.eliassen@veths.no
Brodal
Bjørn P
BP
Svindland
Aud
A
Osmundsen
Harald
H
Rønning
Helle
H
Djurovic
Srdjan
S
Berg
Kåre
K
D042962:Acyl-CoA Oxidase / Q000378:metabolism; D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors; D000818:Animals; D002374:Catalase / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004036:Diet, Atherogenic; D004041:Dietary Fats / Q000008:administration & dosage; D005234:Fatty Liver / Q000139:chemically induced / Q000473:pathology; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D007421:Intestine, Small / Q000201:enzymology / Q000648:ultrastructure; D007668:Kidney / Q000378:metabolism; D017270:Lipoprotein(a) / Q000235:genetics*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D000587:Oxidoreductases Acting on CH-NH Group Donors / Q000378:metabolism; D020675:Peroxisomes / Q000187:drug effects / Q000201:enzymology*; D011073:Polyamines / Q000378:metabolism*; D000097667:Polyamine Oxidase
D042962:Acyl-CoA Oxidase; D006631:Amine Oxidase (Copper-Containing); D002374:Catalase; D002791:Cholesterol, Dietary; D004041:Dietary Fats; D006146:Guanidines; D017270:Lipoprotein(a); D000587:Oxidoreductases Acting on CH-NH Group Donors; D011073:Polyamines; D000097667:Polyamine Oxidase; C004479:pimagedine