Activation of glucose transport during simulated ischemia in H9c2 cardiac myoblasts is mediated by protein kinase C isoforms
Activation of glucose transport during simulated ischemia in H9c2 cardiac myoblasts is mediated by protein kinase C isoforms
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DOI：
10.1016/j.lfs.2005.04.039
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发表时间：
2005-12-05
期刊：
影响因子：
6.1
通讯作者：
Caldarera, CM
中科院分区：
文献类型：
--
作者：
Agnetti, G;Maraldi, T;Caldarera, CM
葡萄糖转运到细胞中可由多种条件调节，包括缺血。我们研究了是否一些酶经常参与代谢适应缺血也需要葡萄糖转运激活。通过在缺氧的无血清和无葡萄糖培养基中孵育3小时H9 c2成心肌细胞来模拟缺血。在这些条件下，2-脱氧-D-[2，6-H-3]-葡萄糖摄取增加（高于对照水平57%，p < 0.0001），与GLUT 1和GLUT 4易位至肌膜一致。酪氨酸激酶抑制剂对模拟缺血诱导的葡萄糖转运上调没有影响。另一方面，白屈菜红碱，一种广泛的蛋白激酶C亚型的抑制剂，和rottlerin，蛋白激酶C δ的抑制剂，完全阻止了运输速率的刺激。在用常规蛋白激酶C的抑制剂Go 6976处理后，己糖摄取的活化较低（19%，p < 0.001）。最后，PD 98059介导的ERK 1/2（一种下游丝裂原活化蛋白激酶（MAPK））磷酸化的抑制仅部分降低模拟缺血诱导的葡萄糖转运的活化（31%，p < 0.01），而p38 MAPK抑制剂SB 203580没有发挥任何作用。这些结果表明，蛋白激酶C δ的刺激是密切相关的培养的心肌细胞中模拟缺血诱导的葡萄糖转运的上调和传统的蛋白激酶C和ERK 1/2部分参与介导这一过程的信号通路。(c)2005年爱思唯尔公司All rights reserved.
Glucose transport into cells may be regulated by a variety of conditions, including ischemia. We investigated whether some enzymes frequently involved in the metabolic adaptation to ischemia are also required for glucose transport activation. Ischemia was simulated by incubating during 3 h H9c2 cardiomyoblasts in a serum- and glucose-free medium in hypoxia. Under these conditions 2-deoxy-D-[2,6-H-3]-glucose uptake was increased (57% above control levels, p < 0.0001) consistently with GLUT1 and GLUT4 translocation to sarcolemma. Tyrosine kinases inhibition via tyrphostin had no effect on glucose transport up-regulation induced by simulated ischemia. On the other hand, chelerythrine, a broad range inhibitor of protein kinase C isoforms, and rottlerin, an inhibitor of protein kinase C delta, completely prevented the stimulation of the transport rate. A lower activation of hexose uptake (19%, p < 0.001) followed also treatment with Go6976, an inhibitor of conventional protein kinases C. Finally, PD98059-mediated inhibition of the phosphorylation of ERK 1/2, a downstream mitogen-activated protein kinase (MAPK), only partially reduced the activation of glucose transport induced by simulated ischemia (31%, p < 0.01), while SB203580, an inhibitor of p38 MAPK, did not exert any effect. These results indicate that stimulation of protein kinase C delta is strongly related to the up-regulation of glucose transport induced by simulated ischemia in cultured cardiomyoblasts and that conventional protein kinases C and ERK 1/2 are partially involved in the signalling pathways mediating this process. (c) 2005 Elsevier Inc. All rights reserved.