Role of GLUT1 in regulation of reactive oxygen species.
Role of GLUT1 in regulation of reactive oxygen species.
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DOI：
10.1016/j.redox.2014.03.004
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发表时间：
2014
期刊：
影响因子：
11.4
通讯作者：
Fisher, Jonathan S.
中科院分区：
文献类型：
--
作者：
Andrisse, Stanley;Koehler, Rikki M.;Chen, Joseph E.;Patel, Gaytri D.;Vallurupalli, Vivek R.;Ratliff, Benjamin A.;Warren, Daniel E.;Fisher, Jonathan S.
关键词：
在骨骼肌细胞中，GLUT 1负责葡萄糖和脱氢抗坏血酸的大部分基础摄取，这两者在抗氧化防御中发挥作用。我们假设，减少GLUT 1介导的转运的条件将导致L 6成肌细胞中活性氧（ROS）水平增加，而增加GLUT 1介导的转运的条件将导致ROS水平降低。我们发现，GLUT 1抑制剂fasentin和根皮素增加抗霉素A和超氧化物发生剂邻苯三酚诱导的ROS水平。然而，茚地那韦抑制GLUT 4而不是GLUT 1，对ROS水平没有影响。共济失调毛细血管扩张突变（ATM）抑制剂和激活剂，以前显示抑制和增强GLUT 1介导的运输，增加和减少ROS水平，分别。GLUT 1（GLUT 1-S490 A）上ATM靶位点的突变增加了ROS水平，并阻止了ATM激活剂多柔比星的ROS降低作用。与此相反，GLUT 1-S490 D的表达降低了ROS水平，在挑战与邻苯三酚，防止增加ROS时，ATM被抑制，并防止邻苯三酚诱导的减少胰岛素信号和胰岛素刺激的葡萄糖转运。总之，这些数据表明，GLUT 1在ROS的调节中起作用，并可能有助于在ROS存在下维持胰岛素作用。抑制GLUT 1，但不抑制GLUT 4，增加成肌细胞中的ROS水平。GLUT 1上的ATM靶位点突变为丙氨酸（GLUT 1-S490 A）会增加ROS。ATM激活剂阿霉素降低ROS，除了在表达GLUT 1-S490 A的细胞中。除了在用GLUT 1 S490 D转染的细胞中，ATM的抑制增加了ROS。GLUT 1-S490 D的表达保护细胞免受ROS介导的胰岛素抵抗。
In skeletal muscle cells, GLUT1 is responsible for a large portion of basal uptake of glucose and dehydroascorbic acid, both of which play roles in antioxidant defense. We hypothesized that conditions that would decrease GLUT1-mediated transport would cause increased reactive oxygen species (ROS) levels in L6 myoblasts, while conditions that would increase GLUT1-mediated transport would result in decreased ROS levels. We found that the GLUT1 inhibitors fasentin and phloretin increased the ROS levels induced by antimycin A and the superoxide generator pyrogallol. However, indinavir, which inhibits GLUT4 but not GLUT1, had no effect on ROS levels. Ataxia telangiectasia mutated (ATM) inhibitors and activators, previously shown to inhibit and augment GLUT1-mediated transport, increased and decreased ROS levels, respectively. Mutation of an ATM target site on GLUT1 (GLUT1-S490A) increased ROS levels and prevented the ROS-lowering effect of the ATM activator doxorubicin. In contrast, expression of GLUT1-S490D lowered ROS levels during challenge with pyrogallol, prevented an increase in ROS when ATM was inhibited, and prevented the pyrogallol-induced decrease in insulin signaling and insulin-stimulated glucose transport. Taken together, the data suggest that GLUT1 plays a role in regulation of ROS and could contribute to maintenance of insulin action in the presence of ROS. Inhibition of GLUT1, but not inhibition of GLUT4, increases ROS levels in myoblasts. Mutation of an ATM target site on GLUT1 to alanine (GLUT1-S490A) increases ROS. The ATM activator doxorubicin decreases ROS except in cells that express GLUT1-S490A. Inhibition of ATM increases ROS except in cells transfected with GLUT1S490D. Expression of GLUT1-S490D protects cells against ROS-mediated insulin resistance.
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影响因子：
4.1
作者：
GILLMAN, J;NORTON, KB;SUTTON, DA
通讯作者：
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影响因子：
5.9
作者：
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通讯作者：
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DOI：
10.18632/aging.100521
发表时间：
2012-12
期刊：
Aging
影响因子：
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通讯作者：
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影响因子：
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作者：
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影响因子：
64.8
作者：
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