Habets Daphna D J, Coumans Will A, Voshol Peter J, den Boer Marion A M, Febbraio Maria, Bonen Arend, Glatz Jan F C, Luiken Joost J F P
Department of Molecular Genetics, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, P.O. Box 616, 6200 MD Maastricht, The Netherlands.
Biochem Biophys Res Commun. 2007 Mar 30;355(1):204-10. doi: 10.1016/j.bbrc.2007.01.141. Epub 2007 Feb 2.
CD36, also named fatty acid translocase, has been identified as a putative membrane transporter for long-chain fatty acids (LCFA). In the heart, contraction-induced 5' AMP-activated protein kinase (AMPK) signaling regulates cellular LCFA uptake through translocation of CD36 and possibly of other LCFA transporters from intracellular storage compartments to the sarcolemma. In this study, isolated cardiomyocytes from CD36(+/+)- and CD36(-/-) mice were used to investigate to what extent basal and AMPK-mediated LCFA uptake are CD36-dependent. Basal LCFA uptake was not altered in CD36(-/-) cardiomyocytes, most likely resulting from a (1.8-fold) compensatory upregulation of fatty acid-transport protein-1. The stimulatory effect of contraction-mimetic stimuli, oligomycin (2.5-fold) and dipyridamole (1.6-fold), on LCFA uptake into CD36(+/+) cardiomyocytes was almost completely lost in CD36(-/-) cardiomyocytes, despite that AMPK signaling was fully intact. CD36 is almost entirely responsible for AMPK-mediated stimulation of LCFA uptake in cardiomyocytes, indicating a pivotal role for CD36 in mediating changes in cardiac LCFA fluxes.
CD36，也被称为脂肪酸转运蛋白，已被确定为长链脂肪酸（LCFA）的一种假定膜转运体。在心脏中，收缩诱导的5' 腺苷酸活化蛋白激酶（AMPK）信号通路通过CD36以及可能其他LCFA转运体从细胞内储存区室向肌膜的转位来调节细胞对LCFA的摄取。在本研究中，使用来自CD36(+/+)和CD36(-/-)小鼠的分离心肌细胞来研究基础和AMPK介导的LCFA摄取在多大程度上依赖于CD36。CD36(-/-)心肌细胞的基础LCFA摄取没有改变，这很可能是由于脂肪酸转运蛋白-1的（1.8倍）代偿性上调所致。尽管AMPK信号通路完全完整，但模拟收缩刺激物寡霉素（2.5倍）和双嘧达莫（1.6倍）对CD36(+/+)心肌细胞LCFA摄取的刺激作用在CD36(-/-)心肌细胞中几乎完全丧失。CD36几乎完全负责AMPK介导的心肌细胞对LCFA摄取的刺激，表明CD36在介导心脏LCFA通量变化中起关键作用。
