Accelerated rates of glycolysis in the hypertrophied heart: are they a methodological artifact?
Glycolysis, measured by (3)H(2)O production from [5-(3)H]glucose, is accelerated in isolated working hypertrophied rat hearts. However, nonglycolytic detritiation of [5-(3)H]glucose via the nonoxidative pentose phosphate pathway (PPP) could potentially lead to an overestimation of true glycolytic rates, especially in hypertrophied hearts where the PPP may be upregulated. To address this concern, we measured glycolysis using [5-(3)H]glucose and a second, independent method in isolated working hearts from halothane-anesthetized, sham-operated and aortic-constricted rats. Glycolysis was accelerated in hypertrophied hearts compared with control hearts regardless of the method used. There was also excellent concordance in glycolytic rates between the different methods. Moreover, activity of glucose-6-phosphate dehydrogenase and expression of transaldolase, enzymes controlling key steps in the oxidative and nonoxidative PPP, respectively, were not different between control and hypertrophied hearts. Thus nonglycolytic detritiation of [5-(3)H]glucose in the PPP is insignificant, and (3)H(2)O production from [5-(3)H]glucose is an accurate means to measure glycolysis in isolated working normal and hypertrophied rat hearts. Furthermore, the PPP does not appear to be increased in cardiac hypertrophy induced by abdominal aortic constriction.
Leong
Hon Sing
HS
McDonald Research Laboratories/The iCAPTUR, University of British Columbia-St. Paul's Hospital, Vancouver, British Columbia, V6Z 1Y6.
Grist
Mark
M
Parsons
Hannah
H
Wambolt
Richard B
RB
Lopaschuk
Gary D
GD
Brownsey
Roger
R
Allard
Michael F
MF
D000818:Animals; D016477:Artifacts; D001794:Blood Pressure; D005947:Glucose / Q000493:pharmacokinetics; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006019:Glycolysis / Q000502:physiology*; D006339:Heart Rate; D017379:Hypertrophy, Left Ventricular / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D019344:Lactic Acid / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000201:enzymology / Q000473:pathology; D009929:Organ Size; D010084:Oxidation-Reduction; D010427:Pentose Phosphate Pathway / Q000502:physiology; D019289:Pyruvic Acid / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014153:Transaldolase / Q000378:metabolism; D014316:Tritium
D014316:Tritium; D019344:Lactic Acid; D019289:Pyruvic Acid; D005954:Glucosephosphate Dehydrogenase; D014153:Transaldolase; D005947:Glucose