Reduced insulin/insulin-like growth factor-1 signaling and dietary restriction inhibit translation but preserve muscle mass in Caenorhabditis elegans.
Reduced insulin/insulin-like growth factor-1 signaling and dietary restriction inhibit translation but preserve muscle mass in Caenorhabditis elegans.
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DOI：
10.1074/mcp.m113.027383
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发表时间：
2013-12
期刊：
影响因子：
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通讯作者：
Braeckman BP
中科院分区：
文献类型：
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作者：
Depuydt G;Xie F;Petyuk VA;Shanmugam N;Smolders A;Dhondt I;Brewer HM;Camp DG 2nd;Smith RD;Braeckman BP
通过C. Elegans胰岛素/胰岛素样生长因子-1-样酪氨酸激酶受体DAF-2和通过细菌稀释的饮食限制是两种充分表征的延长寿命的干预措施，其平行或通过（部分）独立的机制起作用。使用精确的质量和时间标签LC-MS/MS定量蛋白质组学，我们检测到大量的核糖体亚基的丰度减少，在响应饮食限制，以及在daf-2（e1370）胰岛素/胰岛素样生长因子-1-受体突变体。此外，这些长寿蠕虫的一般蛋白质合成水平受到抑制。令人惊讶的是，核糖体转录水平与实际蛋白质丰度无关，这表明转录后调节决定核糖体含量。蛋白质组学还揭示了长寿蠕虫中许多结构性肌细胞成分的增加，这似乎是由于在营养不良或低胰岛素样信号传导条件下优先保存肌细胞体积所致。激活β-16，而不是饮食限制，刺激肌肉相关基因的mRNA表达，以防止肌肉萎缩。重要的daf-2特异性蛋白质组变化包括有氧代谢酶的过度表达和应激反应和免疫防御系统的普遍激活，而蛋白酶体核心复合物的许多蛋白质亚基丰度的增加是饮食限制特异性特征。
Reduced signaling through the C. elegans insulin/insulin-like growth factor-1-like tyrosine kinase receptor daf-2 and dietary restriction via bacterial dilution are two well-characterized lifespan-extending interventions that operate in parallel or through (partially) independent mechanisms. Using accurate mass and time tag LC-MS/MS quantitative proteomics, we detected that the abundance of a large number of ribosomal subunits is decreased in response to dietary restriction, as well as in the daf-2(e1370) insulin/insulin-like growth factor-1-receptor mutant. In addition, general protein synthesis levels in these long-lived worms are repressed. Surprisingly, ribosomal transcript levels were not correlated to actual protein abundance, suggesting that post-transcriptional regulation determines ribosome content. Proteomics also revealed the increased presence of many structural muscle cell components in long-lived worms, which appeared to result from the prioritized preservation of muscle cell volume in nutrient-poor conditions or low insulin-like signaling. Activation of DAF-16, but not diet restriction, stimulates mRNA expression of muscle-related genes to prevent muscle atrophy. Important daf-2-specific proteome changes include overexpression of aerobic metabolism enzymes and general activation of stress-responsive and immune defense systems, whereas the increased abundance of many protein subunits of the proteasome core complex is a dietary-restriction-specific characteristic.