Critical role for lactate dehydrogenase A in aerobic glycolysis that sustains pulmonary microvascular endothelial cell proliferation
Critical role for lactate dehydrogenase A in aerobic glycolysis that sustains pulmonary microvascular endothelial cell proliferation
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DOI：
10.1152/ajplung.00274.2009
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发表时间：
2010-10-01
影响因子：
4.9
通讯作者：
Stevens, Troy
中科院分区：
文献类型：
--
作者：
Parra-Bonilla, Glenda;Alvarez, Diego F.;Stevens, Troy
[10]杨晓波，王晓波.乳酸脱氢酶A在维持肺微血管内皮细胞增殖的有氧糖酵解中的关键作用。美国生理学杂志肺细胞分子生理学299：L513-L522，2010年。首次发表于2010年7月30日; doi：10.1152/ajplung.00274.2009。肺微血管内皮细胞具有高度增殖和血管生成能力，但目前尚不清楚这些细胞如何维持这种生长所必需的代谢要求。快速增殖的细胞依靠有氧糖酵解来维持生长，其特征在于葡萄糖消耗、葡萄糖发酵成乳酸盐和乳酸酸中毒，所有这些都是在足够的氧浓度存在下进行的。乳酸脱氢酶A将丙酮酸转化为维持糖酵解快速流动所必需的乳酸。因此，我们检验了肺微血管内皮细胞表达乳酸脱氢酶A的假设，乳酸脱氢酶A是利用有氧糖酵解和支持其生长所必需的。肺微血管内皮细胞（PMVEC）的生长曲线进行了7天的时间。PMVEC消耗葡萄糖，将葡萄糖转化为乳酸盐，并酸化培养基。限制细胞外葡萄糖消除乳酸酸中毒和减少PMVEC的生长，取代葡萄糖与半乳糖。相反，缓慢生长的肺动脉内皮细胞（PAECs）消耗的葡萄糖最少，在整个生长曲线中没有出现乳酸酸中毒。PAEC的耗氧量是PMVEC的两倍，但总细胞ATP浓度是PMVEC的两倍。葡萄糖转运蛋白1，己糖激酶-2，乳酸脱氢酶A都上调PMVEC相比，其大血管的同行。抑制乳酸脱氢酶A的活性和表达防止乳酸酸中毒和减少PMVEC的生长。因此，PMVEC利用有氧糖酵解来维持其快速生长速率，这依赖于乳酸脱氢酶A。
Parra-Bonilla G, Alvarez DF, Al-Mehdi AB, Alexeyev M, Stevens T. Critical role for lactate dehydrogenase A in aerobic glycolysis that sustains pulmonary microvascular endothelial cell proliferation. Am J Physiol Lung Cell Mol Physiol 299: L513-L522, 2010. First published July 30, 2010; doi:10.1152/ajplung.00274.2009.-Pulmonary microvascular endothelial cells possess both highly proliferative and angiogenic capacities, yet it is unclear how these cells sustain the metabolic requirements essential for such growth. Rapidly proliferating cells rely on aerobic glycolysis to sustain growth, which is characterized by glucose consumption, glucose fermentation to lactate, and lactic acidosis, all in the presence of sufficient oxygen concentrations. Lactate dehydrogenase A converts pyruvate to lactate necessary to sustain rapid flux through glycolysis. We therefore tested the hypothesis that pulmonary microvascular endothelial cells express lactate dehydrogenase A necessary to utilize aerobic glycolysis and support their growth. Pulmonary microvascular endothelial cell (PMVEC) growth curves were conducted over a 7-day period. PMVECs consumed glucose, converted glucose into lactate, and acidified the media. Restricting extracellular glucose abolished the lactic acidosis and reduced PMVEC growth, as did replacing glucose with galactose. In contrast, slow-growing pulmonary artery endothelial cells (PAECs) minimally consumed glucose and did not develop a lactic acidosis throughout the growth curve. Oxygen consumption was twofold higher in PAECs than in PMVECs, yet total cellular ATP concentrations were twofold higher in PMVECs. Glucose transporter 1, hexokinase-2, and lactate dehydrogenase A were all upregulated in PMVECs compared with their macrovascular counterparts. Inhibiting lactate dehydrogenase A activity and expression prevented lactic acidosis and reduced PMVEC growth. Thus PMVECs utilize aerobic glycolysis to sustain their rapid growth rates, which is dependent on lactate dehydrogenase A.