Metabolic inhibition potentiates oxidant injury.
Metabolic inhibition potentiates oxidant injury.
复制标题
代谢抑制会加剧氧化损伤。
DOI：
10.1016/0022-4804(91)90197-t
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发表时间：
1991
期刊：
影响因子：
--
通讯作者：
D. Hinshaw
中科院分区：
文献类型：
--
作者：
R. Delius;D. Hinshaw
毒性氧类已被认为是缺血器官再灌注后损伤的重要介质。本研究的目的是确定先前的代谢抑制，如缺血期间发生的代谢抑制，是否增强体外氧化损伤。牛肺动脉内皮细胞代谢抑制不同的时间段与或没有线粒体抑制剂寡霉素（650 nM）。通过洗涤步骤和随后加入5.5 mM葡萄糖将细胞从代谢抑制中拯救出来。在代谢抑制缓解的同时，细胞经受剂量范围为0至100 μM的H2 O2。ATP水平监测超过2小时的时间过程后，从救援代谢抑制，通过荧光素酶测定。通过台盼蓝拒染法评估代谢抑制缓解后2小时的细胞活力。用荧光染料2′，7 ′-双-（2-羧乙基）-5（和-6）羧基荧光素四乙酰甲氧基甲酯测定代谢抑制期间的细胞内pH。H2 O2消耗，一个衡量H2 O2清除能力，测定通过荧光测定。未受到代谢抑制的细胞的活力和ATP水平不受这些低浓度H2 O2的影响。细胞代谢抑制与葡萄糖耗竭和寡霉素是精致敏感的H2 O2。仅剥夺葡萄糖的细胞没有表现出损伤的增强，而单独用寡霉素进行线粒体抑制的细胞也表现出氧化损伤的显著增强。H2 O2消耗量不受代谢抑制的影响。与线粒体抑制相关的条件一致导致细胞内pH值的降低。这些实验表明，代谢抑制和随后的氧化剂暴露之间存在协同作用。这种协同作用依赖于线粒体功能的抑制，但不依赖于ATP水平。细胞内酸中毒与加强氧化损伤的条件密切相关。
Toxic oxygen species have been implicated as important mediators of injury after reperfusion of an ischemic organ. The aim of this study was to determine if prior metabolic inhibition, such as that which occurs during ischemia, potentiates oxidant injuryin vitro. Bovine pulmonary artery endothelial cells were metabolically inhibited for various periods of time with or without the mitochondrial inhibitor oligomycin (650 nM). The cells were rescued from metabolic inhibition by a wash step and subsequent addition of 5.5 mMglucose. At the same time that metabolic inhibition was relieved the cells were subjected to doses of H2O2ranging from 0 to 100 μM. ATP levels were monitored over a 2-hr time course after rescue from metabolic inhibition by the luciferin—luciferase assay. Cell viability at 2 hr after relief of metabolic inhibition was assessed by trypan blue exclusion. Intracellular pH during metabolic inhibition was determined with the fluorescent dye 2′,7′-bis-(2-carboxyethyl)-5(and-6) carboxyfluorescein tetraacetomethoxymethyl ester. H2O2consumption, a measure of H2O2scavenging capability, was determined by a fluorescent assay. The viability and ATP levels of cells not subjected to metabolic inhibition were unaffected by these low concentrations of H2O2. Cells metabolically inhibited with glucose depletion and oligomycin were exquisitely sensitive to H2O2. Cells that were only deprived of glucose demonstrated no potentiation of injury, while cells subjected to mitochondrial inhibition with oligomycin alone also showed significant potentiation of oxidant injury. H2O2consumption was not affected by metabolic inhibition. Conditions associated with mitochondrial inhibition consistently resulted in a decrease in intracellular pH. These experiments suggest that a synergism exists between metabolic inhibition and subsequent oxidant exposure. This synergism is dependent on inhibition of mitochondrial function but is independent of ATP levels. Intracellular acidosis correlated well with conditions which potentiated oxidant injury.
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影响因子：
15.9
作者：
GORES, GJ;NIEMINEN, AL;LEMASTERS, JJ
通讯作者：
LEMASTERS, JJ
DOI：
10.1016/s0021-9258(19)77928-9
发表时间：
1988-02
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
P. Hyslop;Daniel;Hinshawz;Wayne A. Halsey;Ingrid;Schraufstatter;Richard D. Sauerhebery;Roger G. Spraggj;Janis H. Jackson;C G Cochrane
通讯作者：
P. Hyslop;Daniel;Hinshawz;Wayne A. Halsey;Ingrid;Schraufstatter;Richard D. Sauerhebery;Roger G. Spraggj;Janis H. Jackson;C G Cochrane
影响因子：
15.9
作者：
SPRAGG, RG;HINSHAW, DB;COCHRANE, CG
通讯作者：
COCHRANE, CG
影响因子：
15.9
作者：
SCHRAUFSTATTER, I;HYSLOP, PA;COCHRANE, CG
通讯作者：
COCHRANE, CG