Document Detail

Involvement of lysosome-like particles in the metabolism of endogenous myocardial triglycerides during ischemia/reperfusion. Uptake and degradation of triglycerides by lysosomes isolated from rat heart.
MedLine Citation:
PMID:  2350329     Owner:  NLM     Status:  MEDLINE    
The hormonal regulation and enzymatic basis of endogenous lipolysis in heart are not yet completely elucidated. The lysosomal fraction from rat heart appeared to be markedly enriched in triglycerides and a significant reduction in triglycerides in this fraction was found after prolonged perfusion or stimulation of lipolysis with glucagon. The enhanced rate of lipolysis, measured as glycerol release from the isolated perfused rat heart, was abolished 10-15 min after continuous glucagon administration. Omission of glucagon for another 60 min restored the ability of glucagon to stimulate lipolysis, indicating the limited availability of endogenous triglycerides and the presence of a transfer-system for triglycerides from a non-metabolically active pool to a metabolically active pool. The enhanced lipolysis induced by low-flow ischemia was found to be inhibited by the lysosomotropic agent methylamine (5 mM). Methylamine-perfusion during low-flow ischemia was accompanied by an increased recovery of myocardial triglycerides in the lysosomal fraction. The possible role of lysosome-like particles in myocardial triglyceride homeostasis was further investigated by studying the kinetics of uptake and degradation of labeled triglycerides by membrane-particles recovered in the subcellular fraction enriched with lysosomal marker enzymes. It appeared that isolated lysosomal membranes take up added triglycerides at an average rate of 30 nmoles/min/g protein. The bulk of these triglycerides taken up is stored whereas 20% is degraded to diglycerides and free fatty acids. More than 90% of the free fatty acids formed were released from the lysosomes into the supernatant. The uptake and degradation of triglyceride-filled liposomes by isolated myocardial lysosomes was inhibited during incubation with methylamine (5 mM). On the other hand, a lowering of pH during in vitro incubation increased the rate of uptake and degradation of added triglycerides by isolated lysosomes. These results indicate that lysosomes or lysosome-like particles are involved in the enhanced lipolysis during myocardial ischemia.
K Schoonderwoerd; S Broekhoven-Schokker; W C Hülsmann; H Stam
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Basic research in cardiology     Volume:  85     ISSN:  0300-8428     ISO Abbreviation:  Basic Res. Cardiol.     Publication Date:    1990 Mar-Apr
Date Detail:
Created Date:  1990-07-12     Completed Date:  1990-07-12     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0360342     Medline TA:  Basic Res Cardiol     Country:  GERMANY, WEST    
Other Details:
Languages:  eng     Pagination:  153-63     Citation Subset:  IM    
Department of Biochemistry I, Medical Faculty, Erasmus University Rotterdam, The Netherlands.
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MeSH Terms
Acid-Base Equilibrium / physiology
Adenosine Monophosphate / metabolism
Calcium / metabolism
Coronary Circulation / physiology*
Coronary Disease / physiopathology*
Glycerol / metabolism
Lipolysis / physiology
Lysosomes / physiology*
Methylamines / pharmacology
Myocardial Reperfusion
Myocardium / metabolism*
Rats, Inbred Strains
Triglycerides / metabolism*
Reg. No./Substance:
0/Methylamines; 0/Triglycerides; 56-81-5/Glycerol; 61-19-8/Adenosine Monophosphate; 74-89-5/methylamine; 7440-70-2/Calcium

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