丙酮酸脱氢酶与肥大大鼠心脏中葡萄糖氧化的调节
Pyruvate dehydrogenase and the regulation of glucose oxidation in hypertrophied rat hearts.
作者信息
Lydell Carmen P, Chan Andy, Wambolt Richard B, Sambandam Nandakumar, Parsons Hannah, Bondy Gregory P, Rodrigues Brian, Popov Kirill M, Harris Robert A, Brownsey Roger W, Allard Michael F
机构信息
McDonald Research Laboratories/The iCapture Centre, Department of Pathology and Laboratory Medicine, Room 292, University of British Columbia-St. Paul's Hospital, 1081 Burrand Street, Vancouver, BC, Canada V6Z 1Y6.
出版信息
Cardiovasc Res. 2002 Mar;53(4):841-51. doi: 10.1016/s0008-6363(01)00560-0.
OBJECTIVE
Coupling of glucose oxidation to glycolysis is lower in hypertrophied than in non-hypertrophied hearts, contributing to the compromised mechanical performance of hypertrophied hearts. Here, we describe studies to test the hypothesis that low coupling of glucose oxidation to glycolysis in hypertrophied hearts is due to reduced activity and/or expression of the pyruvate dehydrogenase complex (PDC).
METHODS
We examined the effects of dichloroacetate (DCA), an inhibitor of PDC kinase, and of alterations in exogenous palmitate supply on coupling of glucose oxidation to glycolysis in isolated working hypertrophied and control hearts from aortic-constricted and sham-operated male Sprague-Dawley rats. It was anticipated that the addition of DCA or the absence of palmitate would promote PDC activation and consequently normalize coupling between glycolysis and glucose oxidation in hypertrophied hearts if our hypothesis was correct.
RESULTS
Addition of DCA or removal of palmitate improved coupling of glucose oxidation to glycolysis in control and hypertrophied hearts. However, coupling remained substantially lower in hypertrophied hearts. PDC activity in extracts of hypertrophied hearts was similar to or higher than in extracts of control hearts under all perfusion conditions. No differences were observed between hypertrophied and control hearts with respect to expression of PDC, PDC kinase, or PDC phosphatase.
CONCLUSIONS
Low coupling of glucose oxidation to glycolysis in hypertrophied hearts is not due to a reduction in PDC activity or subunit expression indicating that other mechanism(s) are responsible.
目的
与非肥厚型心脏相比，肥厚型心脏中葡萄糖氧化与糖酵解的偶联作用更低，这导致了肥厚型心脏机械性能受损。在此，我们描述了一些研究，以检验以下假设：肥厚型心脏中葡萄糖氧化与糖酵解的低偶联是由于丙酮酸脱氢酶复合体（PDC）活性降低和/或表达减少所致。
方法
我们研究了二氯乙酸（DCA，一种PDC激酶抑制剂）以及外源性棕榈酸供应变化对来自主动脉缩窄和假手术的雄性Sprague-Dawley大鼠的离体工作肥厚型心脏和对照心脏中葡萄糖氧化与糖酵解偶联的影响。如果我们的假设正确，预计添加DCA或缺乏棕榈酸会促进PDC激活，从而使肥厚型心脏中糖酵解与葡萄糖氧化之间的偶联正常化。
结果
添加DCA或去除棕榈酸可改善对照心脏和肥厚型心脏中葡萄糖氧化与糖酵解的偶联。然而，肥厚型心脏中的偶联仍显著更低。在所有灌注条件下，肥厚型心脏提取物中的PDC活性与对照心脏提取物中的相似或更高。在PDC、PDC激酶或PDC磷酸酶的表达方面，肥厚型心脏与对照心脏之间未观察到差异。
结论
肥厚型心脏中葡萄糖氧化与糖酵解的低偶联并非由于PDC活性或亚基表达降低，这表明存在其他机制。
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