Effects of microgravity on osteoblast mitochondria: a proteomic and metabolomics profile.
Effects of microgravity on osteoblast mitochondria: a proteomic and metabolomics profile.
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DOI：
10.1038/s41598-017-15612-1
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发表时间：
2017-11-13
影响因子：
4.6
通讯作者：
Zolla L
中科院分区：
文献类型：
--
作者：
Michaletti A;Gioia M;Tarantino U;Zolla L
人类原代成骨细胞暴露于模拟微重力环境下的反应已被研究，代谢组学和蛋白质组学分析表明，线粒体稳态明显失调。重力卸载处理导致线粒体蛋白减少，主要影响呼吸链的效率。代谢组学分析显示微重力影响了几种代谢途径；刺激糖酵解和戊糖磷酸途径，而克雷布斯循环在琥珀酸-富马酸转化过程中被中断。有趣的是，蛋白质组学分析显示，催化这一步骤生物转化的线粒体呼吸链复合体II的代表性不足50%。相应地，测定了醌9和醌10的下调。复合物III上调60%，复合物IV下调14%，并伴有ATP质子转运合成的减少。最后，微重力处理诱导氧化应激反应，表现为氧化谷胱甘肽和抗氧化酶的显著降低。苹果酸脱氢酶的减少导致苹果酸-天冬氨酸穿梭的逆转，导致ATP合成的失调。脂肪酸的β -氧化被抑制，促进甘油三酯的产生，同时减少甘油穿梭。综上所述，我们的研究结果表明，微重力可能会抑制骨细胞的功能，损害线粒体的能量势和细胞的能量状态。
The response of human primary osteoblasts exposed to simulated microgravity has been investigated and analysis of metabolomic and proteomic profiles demonstrated a prominent dysregulation of mitochondrion homeostasis. Gravitational unloading treatment induced a decrease in mitochondrial proteins, mainly affecting efficiency of the respiratory chain. Metabolomic analysis revealed that microgravity influenced several metabolic pathways; stimulating glycolysis and the pentose phosphate pathways, while the Krebs cycle was interrupted at succinate-fumarate transformation. Interestingly, proteomic analysis revealed that Complex II of the mitochondrial respiratory chain, which catalyses the biotransformation of this step, was under-represented by 50%. Accordingly, down-regulation of quinones 9 and 10 was measured. Complex III resulted in up-regulation by 60%, while Complex IV was down-regulated by 14%, accompanied by a reduction in proton transport synthesis of ATP. Finally, microgravity treatment induced an oxidative stress response, indicated by significant decreases in oxidised glutathione and antioxidant enzymes. Decrease in malate dehydrogenase induced a reverse in the malate-aspartate shuttle, contributing to dysregulation of ATP synthesis. Beta-oxidation of fatty acids was inhibited, promoting triglyceride production along with a reduction in the glycerol shuttle. Taken together, our findings suggest that microgravity may suppress bone cell functions, impairing mitochondrial energy potential and the energy state of the cell.
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影响因子：
--
作者：
JEE, WSS;WRONSKI, TJ;KIMMEL, DB
通讯作者：
KIMMEL, DB
影响因子：
3.3
作者：
Connor, MK;Hood, DA
通讯作者：
Hood, DA
影响因子：
2.8
作者：
Ciofani, Gianni;Ricotti, Leonardo;Monici, Monica
通讯作者：
Monici, Monica
影响因子：
64.8
作者：
Chouchani, Edward T.;Pell, Victoria R.;Gaude, Edoardo;Aksentijevic, Dunja;Sundier, Stephanie Y.;Robb, Ellen L.;Logan, Angela;Nadtochiy, Sergiy M.;Ord, Emily N. J.;Smith, Anthony C.;Eyassu, Filmon;Shirley, Rachel;Hu, Chou-Hui;Dare, Anna J.;James, Andrew M.;Rogatti, Sebastian;Hartley, Richard C.;Eaton, Simon;Costa, Ana S. H.;Brookes, Paul S.;Davidson, Sean M.;Duchen, Michael R.;Saeb-Parsy, Kourosh;Shattock, Michael J.;Robinson, Alan J.;Work, Lorraine M.;Frezza, Christian;Krieg, Thomas;Murphy, Michael P.
通讯作者：
Murphy, Michael P.
影响因子：
4.1
作者：
Collet, P;Uebelhart, D;Alexandre, C
通讯作者：
Alexandre, C