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Divergent lactate dehydrogenase isoenzyme profile in cellular compartments of primate forebrain structures.
Molecular and Cellular Neuroscience ( IF 2.6 ) Pub Date : 2017-04-29 , DOI: 10.1016/j.mcn.2017.04.007
Tetyana Duka 1 , Zachary Collins 1 , Sarah M Anderson 1 , Mary Ann Raghanti 2 , John J Ely 3 , Patrick R Hof 4 , Derek E Wildman 5 , Morris Goodman 6 , Lawrence I Grossman 6 , Chet C Sherwood 1
Affiliation  

The compartmentalization and association of lactate dehydrogenase (LDH) with specific cellular structures (e.g., synaptosomal, sarcoplasmic or mitochondrial) may play an important role in brain energy metabolism. Our previous research revealed that LDH in the synaptosomal fraction shifts toward the aerobic isoforms (LDH-B) among the large-brained haplorhine primates compared to strepsirrhines. Here, we further analyzed the subcellular localization of LDH in primate forebrain structures using quantitative Western blotting and ELISA. We show that, in cytosolic and mitochondrial subfractions, LDH-B expression level was relatively elevated and LDH-A declined in haplorhines compared to strepsirrhines. LDH-B expression in mitochondrial fractions of the neocortex was preferentially increased, showing a particularly significant rise in the ratio of LDH-B to LDH-A in chimpanzees and humans. We also found a significant correlation between the protein levels of LDH-B in mitochondrial fractions from haplorhine neocortex and the synaptosomal LDH-B that suggests LDH isoforms shift from a predominance of A-subunits toward B-subunits as part of a system that spatially buffers dynamic energy requirements of brain cells. Our results indicate that there is differential subcellular compartmentalization of LDH isoenzymes that evolved among different primate lineages to meet the energy requirements in neocortical and striatal cells.

中文翻译:


灵长类动物前脑结构细胞区室中不同的乳酸脱氢酶同工酶谱。



乳酸脱氢酶(LDH)与特定细胞结构(例如突触体、肌浆或线粒体)的区室化和关联可能在脑能量代谢中发挥重要作用。我们之前的研究表明,与链球菌相比,大脑单福莱因灵长类动物突触体部分中的 LDH 向需氧亚型 (LDH-B) 转变。在这里,我们使用定量蛋白质印迹和 ELISA 进一步分析了灵长类动物前脑结构中 LDH 的亚细胞定位。我们发现,与链球菌相比,在胞浆和线粒体亚组分中,单螺旋藻中的 LDH-B 表达水平相对升高,而 LDH-A 表达水平相对下降。新皮质线粒体部分中的 LDH-B 表达优先增加,显示黑猩猩和人类中 LDH-B 与 LDH-A 的比率特别显着上升。我们还发现,来自 haplorhine 新皮质和突触体 LDH-B 的线粒体部分中的 LDH-B 蛋白水平之间存在显着相关性,这表明 LDH 异构体从 A 亚基的优势转向 B 亚基作为空间缓冲系统的一部分。脑细胞的动态能量需求。我们的结果表明,LDH 同工酶存在不同的亚细胞区室化,这些同工酶在不同的灵长类谱系中进化以满足新皮质和纹状体细胞的能量需求。
更新日期:2019-11-01
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