Signalling components involved in contraction-inducible substrate uptake into cardiac myocytes
Signalling components involved in contraction-inducible substrate uptake into cardiac myocytes
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DOI：
10.1079/pns2004333
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发表时间：
2004-05-01
影响因子：
7
通讯作者：
Glatz, JFC
中科院分区：
文献类型：
--
作者：
Luiken, JJFP;Coort, SLM;Glatz, JFC
葡萄糖和长链脂肪酸(LCFA)是心脏和骨骼肌用于支持收缩活动的两种主要底物。在静止的心肌细胞中，葡萄糖转运体GLUT4和可能的LCFA转运体脂肪酸转位酶(FAT)/CD36的很大一部分存储在细胞内。电刺激诱导细胞收缩，通过GLUT4和FAT/CD36移位到肌膜，增加葡萄糖和LCFA的摄取。在心肌细胞中，蛋白激酶A、AMP激活的蛋白激酶(AMPK)、蛋白激酶C(PKC)亚型和细胞外信号调节激酶作为候选信号酶参与了这些转运蛋白的募集以响应收缩。收集的证据排除了PKA的参与，并暗示AMPK和一个(或多个)PKC亚型(S)在收缩诱导的GLUT4和FAT/CD36易位中起重要作用。沿着这一收缩途径的更多成分的解体可以为通过增加心肌和骨骼肌的机械活动来协调调节葡萄糖和LCFA的摄取提供有价值的信息。
Glucose and long-chain fatty acids (LCFA) are two major substrates used by heart and skeletal muscle to support contractile activity. In quiescent cardiac myocytes a substantial portion of the glucose transporter GLUT4 and the putative LCFA transporter fatty acid translocase (FAT)/CD36 are stored in intracellular compartments. Induction of cellular contraction by electrical stimulation results in enhanced uptake of both glucose and LCFA through translocation of GLUT4 and FAT/CD36 respectively to the sarcolemma. The involvement of protein kinase A, AMP-activated protein kinase (AMPK), protein kinase C (PKC) isoforms and the extracellular signal-regulated kinases was evaluated in cardiac myocytes as candidate signalling enzymes involved in recruiting these transporters in response to contraction. The collected evidence excluded the involvement of PKA and implicated an important role for AMPK and for one (or more) PKC isoform(s) in contraction-induced translocation of both GLUT4 and FAT/CD36. The unravelling of further components along this contraction pathway can provide valuable information on the coordinated regulation of the uptake of glucose and of LCFA by an increase in mechanical activity of heart and skeletal muscle.