Turcotte L P, Raney M A, Todd M K
Department of Kinesiology, College of Letters, Arts and Sciences, University of Southern California, Los Angeles, CA 90089, USA.
Acta Physiol Scand. 2005 Jun;184(2):131-9. doi: 10.1111/j.1365-201X.2005.01445.x.
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.
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.
ERK1/2 phosphorylation was increased by 50% (P < 0.05) during ES but the contraction-induced increase was prevented by the addition of PD-98059. Glucose uptake increased by 3.6-fold (P < 0.05) from rest to ES in muscle perfused without PD-98059 and was not affected by the addition of PD-98059 either at rest (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.
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.
本实验旨在研究细胞外信号调节激酶1/2（ERK1/2）信号通路在收缩诱导的肌肉脂肪酸摄取增加中的作用。
将41只雄性Wistar大鼠随机分为静息组或刺激组。在每组中，动物被随机分配接受PD - 98059，一种丝裂原活化蛋白激酶/细胞外信号调节激酶1/2（MEK1/2）的抑制剂，MEK1/2是ERK1/2上游的激酶，并灌注550微摩尔棕榈酸、[14C]棕榈酸、7毫摩尔葡萄糖且无胰岛素。在刺激组中，每隔2秒给予100毫秒的超强刺激序列，持续20分钟。
在电刺激期间，ERK1/2磷酸化增加了50%（P < 0.05），但添加PD - 98059可阻止收缩诱导的增加。在未添加PD - 98059灌注的肌肉中，从静息到电刺激，葡萄糖摄取增加了3.6倍（P < 0.05），并且在静息时（P > 0.05）或电刺激期间（P > 0.05）添加PD - 98059对其均无影响。对于匹配的棕榈酸递送，电刺激使棕榈酸摄取增加了35%（P < 0.05）。PD - 98059在静息时对棕榈酸摄取无影响，但完全消除了电刺激期间棕榈酸摄取的增加。在电刺激期间，质膜FAT/CD36蛋白含量增加了38%（P < 0.05），但添加PD - 98059可阻止收缩诱导的增加。电刺激使AMPK活性增加（P < 0.05），但不受PD - 98059影响。
这些结果首次表明，在肌肉收缩过程中，脂肪酸摄取和质膜FAT/CD36蛋白含量的增加至少部分是由ERK1/2信号通路介导的。
