Gene expression responses over 24 h to lengthening and shortening contractions in human muscle: major changes in CSRP3, MUSTN1, SIX1, and FBXO32

Gene expression responses over 24 h to lengthening and shortening contractions in human muscle: major changes in CSRP3, MUSTN1, SIX1, and FBXO32
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DOI:
10.1152/physiolgenomics.00151.2006
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发表时间:
2007-09-19
影响因子:
4.6
通讯作者:
Rennie, Michael J.
Rennie, Michael J.
中科院分区:
生物学3区
文献类型:
--
作者:
Kostek, Matthew C.;Chen, Yi-Wen;Rennie, Michael J.

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使用延长(离心)收缩的阻力训练比缩短(同心)收缩诱导更大的肌肉尺寸增加,但潜在的分子机制尚不清楚。使用时间表达谱,我们比较了在不同腿的四头肌同时进行的每种类型的收缩的急性发作的24小时内的基因表达的变化。五名健康的年轻男子进行缩短收缩与一条腿,而对侧腿进行延长收缩。在进食状态下,在运动前和运动后3、6和24小时从双腿进行活检。使用定制的Affyesterday MuscleChip进行表达谱分析(n = 3),所述Affyesterday MuscleChip含有与骨骼肌中表达的3,300个已知基因和表达序列标签相似的探针组。我们确定了51个转录差异调节两种运动模式之间。使用无监督层次聚类,我们确定了四个不同的集群,其中三个对应于独特的功能类别(蛋白质合成,应激反应/早期生长,和肌膜结构)。使用定量RT-PCR(n = 5),我们验证了SIX 1(3 h,-1.9倍,P < 0.001)、CSRP 3(6 h,2.9倍,P < 0.05)和MUSTN 1(24 h,4.3倍,P < 0.05)的表达变化(延长/缩短)。我们检测了FBXO 32/atrogin-1/ MAFbx(一种已知的蛋白质分解和肌肉萎缩的调节因子)是否差异表达:该基因在延长收缩后下调(3 h,2.7倍,P <0.05; 6 h,3.3倍,P < 0.05; 24 h,2.3倍,P < 0.05)。结果表明,运动后3小时,收缩延长和缩短就激活了不同的分子途径。分子差异可能有助于使用两种运动模式进行训练的生理适应机制。
Resistance training using lengthening (eccentric) contractions induces greater increases in muscle size than shortening (concentric) contractions, but the underlying molecular mechanisms are not clear. Using temporal expression profiling, we compared changes in gene expression within 24 h of an acute bout of each type of contractions conducted simultaneously in the quadriceps of different legs. Five healthy young men performed shortening contractions with one leg while the contralateral leg performed lengthening contractions. Biopsies were taken from both legs before exercise and 3, 6, and 24 h afterwards, in the fed state. Expression profiling (n = 3) was performed using a custom-made Affymetrix MuscleChip containing probe sets of similar to 3,300 known genes and expressed sequence tags expressed in skeletal muscle. We identified 51 transcripts differentially regulated between the two exercise modes. Using unsupervised hierarchical clustering, we identified four distinct clusters, three of which corresponded to unique functional categories (protein synthesis, stress response/early growth, and sarcolemmal structure). Using quantitative RT-PCR (n = 5), we verified expression changes (lengthening/shortening) in SIX1 (3 h, -1.9-fold, P < 0.001), CSRP3 (6 h, 2.9-fold, P < 0.05), and MUSTN1 (24 h, 4.3-fold, P < 0.05). We examined whether FBXO32/atrogin-1/ MAFbx, a known regulator of protein breakdown and of muscle atrophy was differentially expressed: the gene was downregulated after lengthening contractions (3 h, 2.7-fold, P < 0.05; 6 h, 3.3-fold, P < 0.05; 24 h, 2.3-fold, P < 0.05). The results suggested that lengthening and shortening contractions activated distinct molecular pathways as early as 3 h postexercise. The molecular differences might contribute to mechanisms underlying the physiological adaptations seen with training using the two modes of exercise.