Plomgaard Peter, Penkowa Milena, Leick Lotte, Pedersen Bente K, Saltin Bengt, Pilegaard Henriette
Centre of Inflammation and Metabolism, Dept. of Infectious Diseases, Rigshospitalet, DK-2100 Copenhagen, Denmark.
J Appl Physiol (1985). 2006 Sep;101(3):817-25. doi: 10.1152/japplphysiol.00183.2006. Epub 2006 Jun 22.
The metabolic profile of rodent muscle is generally reflected in the myosin heavy chain (MHC) fiber-type composition. The present study was conducted to test the hypothesis that metabolic gene expression is not tightly coupled with MHC fiber-type composition for all genes in human skeletal muscle. Triceps brachii, vastus lateralis quadriceps, and soleus muscle biopsies were obtained from normally physically active, healthy, young male volunteers, because these muscles are characterized by different fiber-type compositions. As expected, citrate synthase and 3-hydroxyacyl dehydrogenase activity was more than twofold higher in soleus and vastus than in triceps. Contrary, phosphofructokinase and total lactate dehydrogenase (LDH) activity was approximately three- and twofold higher in triceps than in both soleus and vastus. Expression of metabolic genes was assessed by determining the mRNA content of a broad range of metabolic genes. The triceps muscle had two- to fivefold higher MHC IIa, phosphofructokinase, and LDH A mRNA content and two- to fourfold lower MHC I, lipoprotein lipase, CD36, hormone-sensitive lipase, and LDH B and hexokinase II mRNA than vastus lateralis or soleus. Interestingly, such mRNA differences were not evident for any of the genes encoding mitochondrial oxidative proteins, 3-hydroxyacyl dehydrogenase, carnitine palmitoyl transferase I, citrate synthase, alpha-ketogluterate dehydrogenase, and cytochrome c, nor for the transcriptional regulators peroxisome proliferator activator receptor gamma coactivator-1alpha, forkhead box O1, or peroxisome proliferator activator receptor-alpha. Thus the mRNA expression of genes encoding mitochondrial proteins and transcriptional regulators does not seem to be fiber type specific as the genes encoding glycolytic and lipid metabolism genes, which suggests that basal mRNA regulation of genes encoding mitochondrial proteins does not match the wide differences in mitochondrial content of these muscles.
啮齿动物肌肉的代谢特征通常反映在肌球蛋白重链(MHC)纤维类型组成上。本研究旨在验证以下假设:在人类骨骼肌中,并非所有基因的代谢基因表达都与MHC纤维类型组成紧密相关。从正常身体活跃、健康的年轻男性志愿者身上获取肱三头肌、股外侧肌和比目鱼肌活检样本,因为这些肌肉具有不同的纤维类型组成。正如预期的那样,比目鱼肌和股肌中的柠檬酸合酶和3 - 羟酰基辅酶A脱氢酶活性比肱三头肌高两倍多。相反,肱三头肌中的磷酸果糖激酶和总乳酸脱氢酶(LDH)活性分别比比目鱼肌和股肌高约三倍和两倍。通过测定一系列代谢基因的mRNA含量来评估代谢基因的表达。肱三头肌中MHC IIa、磷酸果糖激酶和LDH A的mRNA含量比股外侧肌或比目鱼肌高两到五倍,而MHC I、脂蛋白脂肪酶、CD36、激素敏感性脂肪酶、LDH B和己糖激酶II的mRNA含量则低两到四倍。有趣的是,对于编码线粒体氧化蛋白、3 - 羟酰基辅酶A脱氢酶、肉碱棕榈酰转移酶I、柠檬酸合酶、α - 酮戊二酸脱氢酶和细胞色素c的任何基因,以及转录调节因子过氧化物酶体增殖物激活受体γ共激活因子 - 1α、叉头框O1或过氧化物酶体增殖物激活受体 - α,这种mRNA差异并不明显。因此,编码线粒体蛋白和转录调节因子的基因的mRNA表达似乎不像编码糖酵解和脂质代谢基因的基因那样具有纤维类型特异性,这表明编码线粒体蛋白的基因的基础mRNA调节与这些肌肉中线粒体含量的广泛差异不匹配。