ERK1/2 inhibition prevents contraction-induced increase in plasma membrane FAT/CD36 content and FA uptake in rodent muscle.
ERK1/2 inhibition prevents contraction-induced increase in plasma membrane FAT/CD36 content and FA uptake in rodent muscle.
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DOI：
10.1111/j.1365-201x.2005.01445.x
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发表时间：
2005-06
期刊：
影响因子：
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通讯作者：
L. Turcotte;M. Raney;M. Todd
中科院分区：
文献类型：
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作者：
L. Turcotte;M. Raney;M. Todd
目的探讨细胞外信号调节激酶1/2（extracellularsignal-regulatedkinase 1/2，ERK 1/2）信号通路在收缩诱导的肌肉FA摄取增加中的作用。方法雄性Wistar大鼠41只，随机分为安静组和刺激组。在每组中，动物被随机分配接受PD-98059，一种MAP/ERK激酶1/2（MEK 1/2）的抑制剂，ERK 1/2上游的激酶，并灌注550 μ M棕榈酸酯，[（14）C]棕榈酸酯，7 mM葡萄糖，无胰岛素。刺激组每隔2s给予100 ms的超最大电流刺激20 min。结果在刺激过程中，ERK 1/2磷酸化水平增加50%（P <0.05）;对于匹配的棕榈酸酯递送，ES使棕榈酸酯摄取增加35%（P < 0.05）。PD-98059对静息时棕榈酸摄入没有影响，但完全消除了ES期间棕榈酸摄入的增加。在ES过程中，质膜FAT/CD 36蛋白含量增加了38%（P < 0.05），但PD-98059的加入阻止了收缩诱导的增加。AMPK活性通过ES增加（P < 0.05），但不受PD-98059的影响。结论本实验结果首次表明，骨骼肌收缩过程中FA摄取和细胞膜FAT/CD 36蛋白含量的增加至少部分是由ERK 1/2信号通路介导的。
AIM The purpose of this experiment was to investigate the role of extracellular signal-regulated kinase 1/2 (ERK1/2) signalling in the contraction-induced increase in muscle FA uptake. METHODS Male Wistar rats (n = 41) were randomly assigned to either a resting or stimulated group. Within each group, animals were randomly assigned to receive PD-98059, an inhibitor of MAP/ERK kinase 1/2 (MEK1/2), a kinase upstream of ERK1/2 and perfused with 550 microM palmitate, [(14)C]palmitate, 7 mM glucose, and no insulin. In the stimulated group, electrical stimulation (ES) of supramaximal trains of 100 ms was delivered every 2 s for 20 min. RESULTS ERK1/2 phosphorylation was increased by 50% (P 0.05) or during ES (P > 0.05). For a matched palmitate delivery, ES increased palmitate uptake by 35% (P < 0.05). PD-98059 had no effect on palmitate uptake at rest but completely abolished the increase in palmitate uptake during ES. Plasma membrane FAT/CD36 protein content was increased by 38% during ES (P < 0.05) but the contraction-induced increase was prevented by the addition of PD-98059. AMPK activity was increased by ES (P < 0.05) but was unaffected by PD-98059. CONCLUSION These results show for the first time that the increase in FA uptake and in plasma membrane FAT/CD36 protein content is mediated, at least in part, by the ERK1/2 signalling pathway during muscle contraction.