Impaired secretion of heart lipoprotein lipase in cyclophosphamide-treated rabbit.
Cyclophosphamide administration into fasted rabbits induces a hypertriglyceridaemia and a defect in vascular lipoprotein lipase. Heart LPL activity was more than 50% decreased after antimitotic treatment in fasted animals. The tissue distribution of lipoprotein lipase activity was followed in heart using recycling perfusion. Cyclophosphamide administration resulted in a profound decline in the heparin-releasable lipoprotein lipase activity, concordant with a higher recovery in the residual heart tissue. The effects were more pronounced in fasted than in fed animals. In agreement, the proportion of neosynthesized [35S]methionine-labelled lipoprotein lipase released by heparin was decreased by 50% following antimitotic treatment. The lipolysis of very low density lipoprotein-labelled triacylglycerols was found 2.5-fold reduced in hearts from cyclophosphamide-treated rabbits as compared to controls. These results suggest that a defective secretion of lipoprotein lipase may contribute to the poor expression of lipolytic activity in the vascular bed and to the occurrence of hypertriglyceridaemia during cyclophosphamide treatment.
Lespine
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A
Laboratoire de Biochimie CHU Purpan, Toulouse, France.
Chap
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H
Perret
B
B
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects; D003520:Cyclophosphamide / Q000494:pharmacology*; D005215:Fasting; D006321:Heart / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology; D015228:Hypertriglyceridemia / Q000139:chemically induced / Q000201:enzymology; D008066:Lipolysis; D008071:Lipoprotein Lipase / Q000032:analysis*; D008079:Lipoproteins, VLDL / Q000378:metabolism; D008715:Methionine / Q000378:metabolism; D009206:Myocardium / Q000201:enzymology*; D010477:Perfusion; D011817:Rabbits; D014280:Triglycerides / Q000378:metabolism
D008079:Lipoproteins, VLDL; D014280:Triglycerides; C030106:very low density lipoprotein triglyceride; D003520:Cyclophosphamide; D006493:Heparin; D008715:Methionine; D008071:Lipoprotein Lipase