Investigation on Intestinal Proteins and Drug Metabolizing Enzymes in Simulated Microgravity Rats by a Proteomics Method.
Investigation on Intestinal Proteins and Drug Metabolizing Enzymes in Simulated Microgravity Rats by a Proteomics Method.
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DOI：
10.3390/molecules25194391
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发表时间：
2020-09-24
期刊：
影响因子：
--
通讯作者：
Li Y
中科院分区：
文献类型：
--
作者：
Liu H;Guo J;Li Y;Zhang Y;Wang J;Gao J;Deng Y;Li Y
本研究旨在探讨模拟微重力14天后肠粘膜蛋白质的变化，尤其是肠道药物代谢酶(IDME)的变化。微重力模拟采用Morey-Holton尾悬架模拟。采用非标记定量蛋白质组学方法检测大鼠肠黏膜蛋白质组。共鉴定出335个差异表达蛋白，其中190个差异表达蛋白上调，145个差异表达蛋白下调。生物信息学分析表明，大部分DEPS具有水解酶、氧化还原酶、转移酶、连接酶或裂解酶催化活性。DEPS主要存在于代谢途径中，包括氨基酸、葡萄糖和碳的代谢。此外，有11个DEPS参与了外源药物和外源物质的代谢。鉴于IDME对口服药物的有效性和安全性的重要性，采用免疫印迹法检测大鼠肠黏膜细胞色素P4501A2、细胞色素P4503A2、细胞色素P4501A2、细胞色素P4501A2、乙醇脱氢酶1和谷胱甘肽S转移酶M5的表达。测定ADH、乙醛脱氢酶(ALDH)和谷草转氨酶(GST)活性。与对照组相比，模拟微重力(SMG)组大鼠肺组织中细胞色素P450 1A2、细胞色素P42D1、细胞色素P3A2和细胞色素P3H1的表达分别下降了33.16%、21.93%、48.49%和22.83%。SMG组大鼠GSTM5表达显著上调53.14%，而CYP2E1表达无明显变化。此外，SMG给药14天后，ADH活性降低，而ALDH和GST活性变化不明显。可以得出结论，SMG显著影响了某些IDME的表达和活性，这可能会改变其底物药物在微重力下的有效性或安全性。本研究提供了关于微重力条件下国际海洋生态系统的一些初步资料。它揭示了SMG对肠道代谢的潜在影响，可能有助于了解航天员的肠道健康和药物使用。
The present study aimed to investigate the change of intestinal mucosa proteins, especially the alteration of intestinal drug metabolizing enzymes (IDMEs) following 14-day simulated microgravity. Morey–Holton tail-suspension analog was used to simulate microgravity. Intestinal mucosa proteins of rats were determined by label-free quantitative proteomic strategy. A total of 335 differentially expressed proteins (DEPs) were identified, 190 DEPs were upregulated, and 145 DEPs were downregulated. According to bioinformatic analysis, most of DEPs exhibited hydrolase, oxidoreductase, transferase, ligase, or lyase catalytic activity. DEPs were mainly enriched in metabolic pathways, including metabolism of amino acid, glucose, and carbon. Moreover, 11 of DEPs were involved in exogenous drug and xenobiotics metabolism. Owing to the importance of IDMEs for the efficacy and safety of oral drugs, the expression of cytochrome P450 1A2 (CYP1A2), CYP2D1, CYP3A2, CYP2E1, alcohol dehydrogenase 1 (ADH1), and glutathione S-transferase mu 5 (GSTM5) in rat intestine mucosa was determined by Western-blot. The activity of ADH, aldehyde dehydrogenase (ALDH) and GST was evaluated. Compared with control rats, the expression of CYP1A2, CYP2D1, CYP3A2, and ADH1 in the simulated microgravity (SMG) group of rats were dramatically decreased by 33.16%, 21.93%, 48.49%, and 22.83%, respectively. GSTM5 was significantly upregulated by 53.14% and CYP2E1 expression did not show a dramatical change in SMG group rats. Moreover, 14-day SMG reduced ADH activity, while ALDH and GST activities was not altered remarkably. It could be concluded that SMG dramatically affected the expression and activity of some IDMEs, which might alter the efficacy or safety of their substrate drugs under microgravity. The present study provided some preliminary information on IDMEs under microgravity. It revealed the potential effect of SMG on intestinal metabolism, which may be helpful to understand the intestinal health of astronauts and medication use.
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影响因子：
8.1
作者：
Burke SJ;Batdorf HM;Burk DH;Martin TM;Mendoza T;Stadler K;Alami W;Karlstad MD;Robson MJ;Blakely RD;Mynatt RL;Collier JJ
通讯作者：
Collier JJ
影响因子：
4
作者：
Hatzistergos, Konstantinos E.;Jiang, Zhijie;Hare, Joshua M.
通讯作者：
Hare, Joshua M.
影响因子：
3.5
作者：
Chen, Bo;Li, George Q.;Li, Yujuan
通讯作者：
Li, Yujuan
影响因子：
6.7
作者：
Greenblatt, DJ;von Moltke, LL;Shader, RI
通讯作者：
Shader, RI
影响因子：
0.3
作者：
Hackney, Kyle J.;Brown, William J.;Tennent, David J.
通讯作者：
Tennent, David J.