We have been able to stimulte the activity of a heart triacyglycerol (TG) lipase with cyclic AMP-inducing agents in perfused rat heart and cardiac myocytes. This activation occurs regardless of whether measurements are made on aqueous homogenates or on delipidated heart powders. The enzyme activity was highly correlated with the amount of TG reduction that occurred in the heart. The pH optimum of this hormone sensitive TG hydrolase is 8.1; therefore, it is referred to as an alkaline TG lipase. We have found that elevating cyclic AMP levles also produces a high correlation between enzyme activity and the reduction in myocardial TG content. Addition to cyclic AMP + Mg-ATP to cell-free extracts of rat heart increases TG lipase activity more than 2-fold. Preliminary experiments indicate that this alkaline TG lipase has the characteristics classically described for lipoprotein (LPL). It is the primary purpose of the proposed experiments to begin to determine the mechanisms involved in the regulation of theis myocardial TG lipase. This will be accomplished by completing the following specific aims: a) determine the effect of cyclic AMP, protein kinase, and alkaline phosphatase on the activity of the cardiac TG lipase in broken cell preparations of rat heart; b) compare and contrast the physical characteristics between rat heart intracellular TG lipase and capillary LPL; c) perform a systematic kinetic analysis of pure TG lipase, LPL, enzyme from crude preparations of rat heart, and lipase from crue preparation of rat heart that has been activated by cyclic AMP + Mg -ATP; d) investigate the possible regulation of purified and partially purified preparations of rat heart hormone-sensitive TG lipse from rat heart by phosphorylation; and e) investigate the regulation of heart TG lipase in heart cardiocytes using various adrenegic agents and antibody to the alkaline TC lipase. The data obtained from these experiments should point out possible mechanisms of the hormonal regulation of the intracellular TG lipase. Moreover, these studies should provide us with fundamental insights into myocardial TG metabolism.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
1R01HL038037-01
Application #
3354026
Study Section
Metabolism Study Section (MET)
Project Start
1987-08-01
Project End
1991-07-31
Budget Start
1987-08-01
Budget End
1988-07-31
Support Year
1
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Illinois at Chicago
Department
Type
Other Specialized Schools
DUNS #
121911077
City
Chicago
State
IL
Country
United States
Zip Code
60612
LaDu, M J; Palmer, W K (1994) Expression of lipoprotein lipase during differentiation of cultured L6 muscle cells. Can J Physiol Pharmacol 72:243-7
Johnston, T P; Palmer, W K (1993) Mechanism of poloxamer 407-induced hypertriglyceridemia in the rat. Biochem Pharmacol 46:1037-42
Ladu, M J; Kapsas, H; Palmer, W K (1991) Regulation of lipoprotein lipase in muscle and adipose tissue during exercise. J Appl Physiol 71:404-9
Hopp, J F; Palmer, W K (1991) Effect of glucose and insulin on triacylglycerol metabolism in isolated normal and diabetic skeletal muscle. Metabolism 40:223-5
LaDu, M J; Schultz, C J; Essig, D A et al. (1991) Characterization of serum-stimulated lipoprotein lipase from bovine heart. Int J Biochem 23:405-11
Ladu, M J; Kapsas, H; Palmer, W K (1991) Regulation of lipoprotein lipase in adipose and muscle tissues during fasting. Am J Physiol 260:R953-9
Hopp, J F; Palmer, W K (1990) Electrical stimulation alters fatty acid metabolism in isolated skeletal muscle. J Appl Physiol 68:2473-81
Palmer, W K; Oscai, L B; Bechtel, P J et al. (1990) Dibutyryl cAMP-induced increases in triacylglycerol lipase activity in developing L8 myotube cultures. Can J Physiol Pharmacol 68:689-93
Oscai, L B; Essig, D A; Palmer, W K (1990) Lipase regulation of muscle triglyceride hydrolysis. J Appl Physiol 69:1571-7
Pearsall, D; Palmer, W K (1990) Triacylglycerol metabolism in rat skeletal muscle after exercise. J Appl Physiol 68:2451-6

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