Effects of amino acid methyl esters on cardiac lysosomes and protein degradation.
Perfusion of rat hearts as Langendorff preparations for 20 min with buffer containing 15 mM glucose and either 10 mM methionine methyl ester or 10 mM leucine methyl ester decreased 1) latency of beta-N-acetylglucosaminidase, 2) buoyant density of cardiac lysosomes, 3) the rate of proteolysis, and 4) heart rate and coronary flow. A significant inhibitory effect on proteolysis was not observed during this brief exposure of insulin-treated hearts to the methyl esters. The effects of the methyl esters were reversible when they were washed away. Heart rate and coronary flow returned to control values within 5 min. After 90 min of recovery, lysosomes distributed on Percoll gradients in dense and buoyant bands that were indistinguishable from control hearts. The reversibility of these effects correlated with the net release of either methionine or leucine from hearts exposed to the corresponding methyl ester. During recovery, rates of proteolysis returned toward those observed in control hearts. In insulin-treated hearts, methionine methyl ester inhibited proteolysis during the recovery period, but leucine methyl ester had no effect. These results indicate that exposure to amino acid methyl esters led to swelling of cardiac lysosomes and inhibition of protein degradation. These effects appeared to be related to the amount of free amino acid that was retained.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D005947:Glucose / Q000378:metabolism; D006321:Heart / Q000187:drug effects / Q000502:physiology; D007328:Insulin / Q000494:pharmacology; D007930:Leucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure*; D008297:Male; D008715:Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure*; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D000596:Amino Acids; D007328:Insulin; D011506:Proteins; C034515:phenylalanine methyl ester; C030365:leucine methyl ester; D010649:Phenylalanine; D000255:Adenosine Triphosphate; D008715:Methionine; C038344:methionine methyl ester; D007930:Leucine; D005947:Glucose