Label-free quantitative proteomics of rat liver exposed to simulated microgravity
Label-free quantitative proteomics of rat liver exposed to simulated microgravity
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DOI：
10.1016/j.actaastro.2020.02.007
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发表时间：
2020-05-01
影响因子：
3.5
通讯作者：
Li, Yujuan
中科院分区：
文献类型：
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作者：
Chen, Bo;Li, George Q.;Li, Yujuan
微重力影响肝脏中碳水化合物、脂质和蛋白质的含量。由于肝脏是内源性和外源性化合物的主要代谢器官，因此深入了解微重力对肝脏的影响具有重要意义。因此，本研究采用无标记定量蛋白质组学方法对尾吊模拟微重力（SM）大鼠肝脏进行了分析。结果表明，SM对肝脏代谢功能有明显的干扰作用。短期SM后，氧化营养物质的酶大大增加，因此肝脏中的葡萄糖、非酯脂肪酸和氨基酸被大量消耗。同时，氧化磷酸化蛋白也受到显著调节。因此，从氧解产生的大量电子不能完全转移到分子氧，随后在肝脏中引发强烈的氧化应激。另一方面，抗氧化剂补偿性增加。随着大部分能量代谢蛋白的恢复和抗氧化剂的持续上调，长期SM后肝脏氧化状态恢复到生理水平。此外，参与异源物质代谢的几种酶，如细胞色素P450和UDP-葡萄糖醛酸转移酶也受到SM的持续时间依赖性调节。我们的数据可能有助于了解微重力对肝脏的影响，并将支持载人航天飞行任务保护措施的设计。
Microgravity affects the content of carbohydrates, lipids and proteins in liver. Since liver is the major metabolic organ of endogenous and exogenous compounds, a deep understanding of microgravity-induced effects on liver could be of great importance. Therefore, livers from tail-suspension simulated microgravity (SM) rat model were analyzed using a label-free quantitative proteomic method in the present study. The results indicated that hepatic metabolic functions were obviously disrupted by SM. After short-term SM, enzymes for oxidizing nutrients were greatly increased and thus glucose, non-ester fatty acids and amino acids in liver were heavily consumed. Meanwhile, proteins for oxidative phosphorylation were also remarkably regulated. Therefore, the vast electrons generated from oxygenolysis could not be fully transferred to dioxygen and subsequently strong oxidative stress was triggered in liver. On the other hand, antioxidants were increased compensatorily. With the restoration of most energy-metabolic proteins and the continuous up-regulation of antioxidants, hepatic oxidative status returned to physiological level after long-term SM. Moreover, several enzymes involved in xenobiotic metabolism, such as cytochrome P450s and UDP-glucuronosyltransferases were also regulated by SM in a duration-dependent way. Our data might be helpful in understanding the effects of microgravity on liver and would support the design of protective measures for manned space missions.