NADH/NAD redox state of cytoplasmic glycolytic compartments in vascular smooth muscle

NADH/NAD redox state of cytoplasmic glycolytic compartments in vascular smooth muscle
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DOI:
10.1152/ajpheart.2000.279.6.h2872
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发表时间:
2000-12-01
影响因子:
4.8
通讯作者:
Parrillo, JE
Parrillo, JE
中科院分区:
医学2区
文献类型:
--
作者:
Barron, JT;Gu, LP;Parrillo, JE

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细胞质NADH/NAD氧化还原电位影响血管平滑肌的能量代谢和收缩反应性。胞质溶胶中的NADH/NAD氧化还原状态主要由糖酵解决定,糖酵解在平滑肌中被分成两个功能独立的细胞质区室,其中一个区室为Na+-K+-ATP酶的活性提供燃料。我们研究了不同糖酵解隔室对胞质NADH/NAD氧化还原状态的影响。10 μ M哇巴因抑制Na+-K+-ATP酶导致糖酵解和乳酸产生减少。尽管如此,乳酸/丙酮酸和甘油-3-磷酸/二羟丙酮磷酸(因此NADH/NAD)的糖酵解代谢物氧化还原对的细胞内浓度和细胞质氧化还原状态不变。代谢物氧化还原对和氧化还原电位的恒定浓度归因于1)由于单羧酸B-H+转运蛋白活性降低(继发于H+共转运可用性降低)导致乳酸和丙酮酸外排减少,以及2)乳酸摄取增加(可能还有丙酮酸)从细胞外空间,可能由单羧酸-H+转运蛋白介导,这与Na+-K+-ATPase活性降低有关。我们的结论是,细胞质的两个糖酵解隔室的氧化还原电位保持平衡,细胞质的NADH/NAD氧化还原电位保持恒定的稳定状态,尽管不同的糖酵解通量在细胞质隔室的Na+-K+-ATP酶。
The cytoplasmic NADH/NAD redox potential affects energy metabolism and contractile reactivity of vascular smooth muscle. NADH/NAD redox state in the cytosol is predominately determined by glycolysis, which in smooth muscle is separated into two functionally independent cytoplasmic compartments, one of which fuels the activity of Na+-K+-ATPase. We examined the effect of varying the glycolytic compartments on cystosolic NADH/NAD redox state. Inhibition of Na+-K+-ATPase by 10 muM ouabain resulted in decreased glycolysis and lactate production. Despite this, intracellular concentrations of the glycolytic metabolite redox couples of lactate/pyruvate and glycerol-3-phosphate/dihydroxyacetone phosphate (thus NADH/NAD) and the cytoplasmic redox state were unchanged. The constant concentration of the metabolite redox couples and redox potential was attributed to 1) decreased efflux of lactate and pyruvate due to decreased activity of monocarboxylate B-H+ transporter secondary to decreased availability of H+ for cotransport and 2) increased uptake of lactate (and perhaps pyruvate) from the extracellular space, probably mediated by the monocarboxylate-H+ transporter, which was specifically linked to reduced activity of Na+-K+-ATPase. We concluded that redox potentials of the two glycolytic compartments of the cytosol maintain equilibrium and that the cytoplasmic NADH/NAD redox potential remains constant in the steady state despite varying glycolytic flux in the cytosolic compartment for Na+-K+-ATPase.