Phosphorylation status of pyruvate dehydrogenase distinguishes metabolic phenotypes of cultured rat brain astrocytes and neurons.
Phosphorylation status of pyruvate dehydrogenase distinguishes metabolic phenotypes of cultured rat brain astrocytes and neurons.
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作者：
Halim, Nader D.;Mcfate, Thomas;Mohyeldin, Armed;Okagaki, Peter;Korotchkina, Lioubov G.;Patel, Mulchand S.;Jeoung, Nam Ho;Harris, Robert A.;Schell, Michael J.;Verma, Ajay
神经组织中的葡萄糖代谢被认为是以区域化的方式发生的，星形胶质细胞在糖酵解中起主要作用，神经元是葡萄糖氧化的主要部位。然而，哺乳动物星形胶质细胞和神经元都含有线粒体，目前尚不清楚为什么在培养中神经元氧化葡萄糖、乳酸和丙酮酸的程度比星形胶质细胞大得多。这项研究的目的是确定丙酮酸代谢在培养的神经元和星形胶质细胞中是否存在差异调节。在培养的星形胶质细胞和神经元中，检测了丙酮酸脱氢酶复合体(PDC)的所有成分的表达，PDC是丙酮酸进入Krebs循环的限速步骤。此外，我们还研究了通过蛋白磷酸化来调节两种细胞的PDC酶活性。我们发现，在培养的两种类型的细胞中都表达了pDC的所有成分，但在星形胶质细胞中，pDC的活性通过丙酮酸脱氢酶α亚单位(PDHα)的磷酸化而被强烈抑制。相反，神经元型pDC在磷酸化pdhα水平低得多的情况下接近最大水平。星形胶质细胞PDHα的去磷酸化可恢复pDC活性并降低乳酸的产生。我们的发现表明，星形胶质细胞和神经元的葡萄糖代谢可能比之前认为的要灵活得多。
Glucose metabolism in nervous tissue has been proposed to occur in a compartmentalized manner with astrocytes contributing largely to glycolysis and neurons being the primary site of glucose oxidation. However, mammalian astrocytes and neurons both contain mitochondria and it remains unclear why in culture neurons oxidize glucose, lactate, and pyruvate to a much larger extent than astrocytes. The objective of this study was to determine whether pyruvate metabolism is differentially regulated in cultured neurons vs. astrocytes. Expression of all components of the pyruvate dehydrogenase complex (PDC), the rate-limiting step for pyruvate entry into the Krebs cycle, was determined in cultured astrocytes and neurons. In addition, regulation of PDC enzymatic activity in the two cell types via protein phosphorylation was examined. We show that all components of the PDC are expressed in both cell types in culture but that PDC activity is kept strongly inhibited in astrocytes through phosphorylation of the pyruvate dehydrogenase alpha subunit (PDHα). In contrast, neuronal PDC operates close to maximal levels with much lower levels of phosphorlyated PDHα. Dephosphorylation of astrocytic PDHα restores PDC activity and lowers lactate production. Our findings suggest that the glucose metabolism of astrocytes and neurons may be far more flexible than previously believed.
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影响因子：
2.9
作者：
Jeoung, Nam Ho;Sanghani, Paresh C.;Harris, Robert A.
通讯作者：
Harris, Robert A.
DOI：
10.1016/s1532-0456(03)00082-6
发表时间：
2003-06-01
影响因子：
3.9
作者：
Hassoun, EA;Ray, S
通讯作者：
Ray, S
影响因子：
5.3
作者：
Lebon, V;Petersen, KF;Rothman, DL
通讯作者：
Rothman, DL
影响因子：
5.3
作者：
Escartin, Carole;Pierre, Karin;Bonvento, Gilles
通讯作者：
Bonvento, Gilles
影响因子：
2.9
作者：
Hopper, RK;Carroll, S;Balaban, RS
通讯作者：
Balaban, RS