Stimulation of cardiac glucose transport by inhibitors of oxidative phosphorylation
Stimulation of cardiac glucose transport by inhibitors of oxidative phosphorylation
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DOI：
10.1016/s0024-3205(01)01325-x
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发表时间：
2001-10-05
期刊：
影响因子：
6.1
通讯作者：
Wheeler, TJ
中科院分区：
文献类型：
--
作者：
Colston, VL;Wheeler, TJ
以前我们发现心脏缺氧通过葡萄糖转运蛋白从细胞内膜到质膜的转位刺激葡萄糖转运。我们后来发现，鱼藤酮，氧化磷酸化的抑制剂，也减少细胞内转运。在这里，使用另一种膜分离技术，我们表明，鱼藤酮增加质膜转运蛋白，和另一种呼吸链抑制剂，叠氮化物，类似的行为。因此，它们可能激活与缺氧相同的信号通路。染料木素，酪氨酸激酶抑制剂，抑制胰岛素和叠氮化物刺激的3-O-甲基葡萄糖转运类似的心肌细胞。它还增加了灌流心脏的质膜中的葡萄糖转运蛋白，即使它抑制葡萄糖摄取，表明对膜运输的影响。另一种酪氨酸激酶抑制剂，laviustin A，和环核苷酸依赖性蛋白激酶抑制剂H-8和H-7对基础或叠氮化物刺激的运输几乎没有影响。多粘菌素B是基础转运、胰岛素刺激转运和叠氮化物刺激转运的弱抑制剂。一氧化氮供体和一氧化氮合酶抑制剂对基础和叠氮化物刺激的运输没有影响。结果表明，酪氨酸激酶;蛋白激酶A，G和C;和一氧化氮不参与心脏葡萄糖转运的缺氧激活。(C)2001 Elsevier Science Inc. All rights reserved.
Previously we showed that hypoxia in heart stimulates glucose transport via translocation of glucose transporters from intracellular membranes to the plasma membrane. We later showed that rotenone, an inhibitor of oxidative phosphorylation, also decreased intracellular transporters. Here, using another membrane fractionation technique, we show that rotenone increases plasma membrane transporters, and that another respiratory chain inhibitor, azide, acts similarly. Thus, they likely activate the same signaling pathway as hypoxia. Genistein, a tyrosine kinase inhibitor, inhibited insulin- and azide-stimulated 3-O-methylglucose transport similarly in cardiac myocytes. It also increased glucose transporters in the plasma membranes of perfused hearts even though it inhibited glucose uptake, suggesting effects on membrane trafficking. Another tyrosine kinase inhibitor, lavendustin A, and the cyclic nucleotide-dependent protein kinase inhibitors H-8 and H-7 had little effect on basal or azide-stimulated transport. Polymyxin B was a weak inhibitor of basal, insulin- stimulated, and azide-stimulated transport. A nitric oxide donor and a nitric oxide synthase inhibitor had no effect on basal and azide-stimulated transport. The results indicate that tyrosine kinases; protein kinases A, G, and C; and nitric oxide are not involved in the hypoxic activation of cardiac glucose transport. (C) 2001 Elsevier Science Inc. All rights reserved.