Wilson J, Winter M, Shasby D M
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.
Blood. 1990 Dec 15;76(12):2578-82.
Oxidants can reversibly increase the permeability of endothelium to ions and macromolecules. Oxidants also deplete ATP in cultured endothelial cells. We asked if oxidant-mediated ATP depletion, alone, accounted for the effects of oxidants on endothelial permeability to macromolecules. When porcine pulmonary artery endothelial cells were exposed to 2.5 mmol/LH2O2, ATP was depleted to 31.7% +/- 1.8% of control within 15 minutes and was reduced to 23.1% +/- 2.0% of control after 30 minutes. To determine if this magnitude of ATP depletion could account for the oxidant-induced increase in endothelial permeability to macromolecules, we measured ATP in endothelial cells exposed to metabolic inhibitors of ATP production. We then measured the effects of these metabolic inhibitors on endothelial monolayer permeability to macromolecules. ATP levels were reduced to 44% +/- 4% of control by 12 mmol/L deoxyglucose (DOG) in the absence of glucose and to 2% +/- 1.3% of control by DOG with 25 nmol/L antimycin A in the absence of glucose. Reduction of endothelial cell ATP to these levels with the metabolic inhibitors did not alter the flux of albumin or dextran across the endothelial monolayers. Thus ATP depletion, by itself, does not explain oxidant-induced changes in endothelial permeability to macromolecules.
氧化剂可使内皮对离子和大分子的通透性可逆性增加。氧化剂还会消耗培养的内皮细胞中的三磷酸腺苷（ATP）。我们探究了仅由氧化剂介导的ATP消耗是否可解释氧化剂对内皮对大分子通透性的影响。当猪肺动脉内皮细胞暴露于2.5 mmol/L过氧化氢（H₂O₂）时，15分钟内ATP消耗至对照的31.7%±1.8%，30分钟后降至对照的23.1%±2.0%。为确定这种ATP消耗程度是否可解释氧化剂诱导的内皮对大分子通透性增加，我们测量了暴露于ATP生成代谢抑制剂的内皮细胞中的ATP。然后我们测量了这些代谢抑制剂对内皮单层对大分子通透性的影响。在无葡萄糖情况下，12 mmol/L脱氧葡萄糖（DOG）可使ATP水平降至对照的44%±4%，在无葡萄糖情况下，DOG与25 nmol/L抗霉素A共同作用可使ATP水平降至对照的2%±1.3%。用代谢抑制剂将内皮细胞ATP降至这些水平并未改变白蛋白或葡聚糖跨内皮单层的通量。因此，ATP消耗本身并不能解释氧化剂诱导的内皮对大分子通透性的变化。
