Orexin system is expressed in avian muscle cells and regulates mitochondrial dynamics
Orexin system is expressed in avian muscle cells and regulates mitochondrial dynamics
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DOI：
10.1152/ajpregu.00394.2014
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发表时间：
2015-02-01
影响因子：
2.8
通讯作者：
Dridi, Sami
中科院分区：
文献类型：
--
作者：
Lassiter, Kentu;Greene, Elizabeth;Dridi, Sami
食欲素A和B是主要由下丘脑外侧产生的促氧肽，它们通过两个G蛋白偶联受体（食欲素受体1/2）发出信号，参与哺乳动物几种生理过程的调节。在鸟类（非哺乳脊椎动物）物种中；然而，食欲素的生理作用尚未明确。本研究提供了新的证据，证明食欲素及其相关受体1/2 （ORXR1/2）不仅在鸡肌肉组织和鹌鹑肌肉（QM7）细胞系中表达，而且在QM7细胞中可能是一种分泌蛋白。体外给药重组食欲素A和B （rORX-A和B）在QM7细胞中呈剂量依赖性差异调节pre - pro-orexin表达，rORX-A上调（P < 0.05）， rORX-B下调（P < 0.05）。两种多肽均上调ORXR1的表达，只有高剂量的rORX-B降低ORXR2的表达（P < 0.05）。禽肌细胞中食欲素及其相关受体的存在及其自身系统的调节表明食欲素可能具有自分泌、旁分泌和/或内分泌作用。rORXs差异调节线粒体动力学网络。rORX-A显著诱导了线粒体分裂相关基因（DNM1、MTFP1、MTFR1）的表达，而rORX-B则增加了参与线粒体融合的mitofusin 2、OPA1和OMA1基因的表达。伴随着这些变化，rORXs差异调节了几种线粒体代谢基因（av-UCP、av-ANT、Ski和NRF-1）及其相关转录调节因子（PPAR γ、PPAR α、PGC-1 α、PGC-1 β和FoxO-1）的表达，但不影响ATP合成。综上所述，我们的数据首次证明了食欲素系统在非哺乳动物肌肉中的存在和分泌，以及它在线粒体融合和裂变中的作用，可能是通过线粒体相关基因及其相关转录因子。
Orexin A and B, orexigenic peptides produced primarily by the lateral hypothalamus that signal through two G protein-coupled receptors, orexin receptors 1/2, have been implicated in the regulation of several physiological processes in mammals. In avian (nonmammalian vertebrates) species; however, the physiological roles of orexin are not well defined. Here, we provide novel evidence that not only is orexin and its related receptors 1/2 (ORXR1/2) expressed in chicken muscle tissue and quail muscle (QM7) cell line, orexin appears to be a secretory protein in QM7 cells. In vitro administration of recombinant orexin A and B (rORX-A and B) differentially regulated prepro-orexin expression in a dose-dependent manner with up-regulation for rORX-A (P < 0.05) and down-regulation for rORX-B (P < 0.05) in QM7 cells. While both peptides upregulated ORXR1 expression, only a high dose of rORX-B decreased the expression of ORXR2 (P < 0.05). The presence of orexin and its related receptors and the regulation of its own system in avian muscle cells indicate that orexin may have autocrine, paracrine, and/or endocrine roles. rORXs differentially regulated mitochondrial dynamics network. While rORX-A significantly induced the expression of mitochondrial fission-related genes (DNM1, MTFP1, MTFR1), rORX-B increased the expression of mitofusin 2, OPA1, and OMA1 genes that are involved in mitochondrial fusion. Concomitant with these changes, rORXs differentially regulated the expression of several mitochondrial metabolic genes (av-UCP, av-ANT, Ski, and NRF-1) and their related transcriptional regulators (PPAR gamma, PPAR alpha, PGC-1 alpha, PGC-1 beta, and FoxO-1) without affecting ATP synthesis. Taken together, our data represent the first evidence of the presence and secretion of orexin system in the muscle of nonmammalian species and its role in mitochondrial fusion and fission, probably through mitochondrial-related genes and their related transcription factors.