Proteo-metabolomics reveals compensation between ischemic and non-injured contralateral kidneys after reperfusion.
Proteo-metabolomics reveals compensation between ischemic and non-injured contralateral kidneys after reperfusion.
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DOI：
10.1038/s41598-018-26804-8
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发表时间：
2018-06-04
影响因子：
4.6
通讯作者：
Kessler BM
中科院分区：
文献类型：
--
作者：
Huang H;van Dullemen LFA;Akhtar MZ;Faro ML;Yu Z;Valli A;Dona A;Thézénas ML;Charles PD;Fischer R;Kaisar M;Leuvenink HGD;Ploeg RJ;Kessler BM
缺血和再灌注损伤（IRI）是急性肾损伤（阿基）的主要原因，导致各种损伤的高发病率和死亡率以及慢性肾脏疾病的发展。肾脏对IRI的细胞和分子反应是复杂的，尚未完全了解。在这里，我们使用了一个综合的蛋白质组学和代谢组学的方法来研究IRI对蛋白质丰度和代谢物水平的影响。大鼠肾脏进行45分钟的热缺血，然后4小时和24小时的再灌注，与对侧和单独的健康肾脏作为对照。IRI后肾组织蛋白质组学显示急性期反应、凝血和补体途径以及脂肪酸（FA）信号传导的蛋白质升高。再灌注4 h后，代谢变化已经明显，糖酵解、脂质和脂肪酸水平升高，而线粒体功能和ATP产生在24 h后受损。这种缺陷部分由对侧肾脏补偿。这种代谢平衡抵消了由于受损肾脏中线粒体功能降低而导致的能量不足。
Ischaemia and reperfusion injury (IRI) is the leading cause of acute kidney injury (AKI), which contributes to high morbidity and mortality rates in a wide range of injuries as well as the development of chronic kidney disease. The cellular and molecular responses of the kidney to IRI are complex and not fully understood. Here, we used an integrated proteomic and metabolomic approach to investigate the effects of IRI on protein abundance and metabolite levels. Rat kidneys were subjected to 45 min of warm ischaemia followed by 4 h and 24 h reperfusion, with contralateral and separate healthy kidneys serving as controls. Kidney tissue proteomics after IRI revealed elevated proteins belonging to the acute phase response, coagulation and complement pathways, and fatty acid (FA) signalling. Metabolic changes were already evident after 4 h reperfusion and showed increased level of glycolysis, lipids and FAs, whilst mitochondrial function and ATP production was impaired after 24 h. This deficit was partially compensated for by the contralateral kidney. Such a metabolic balance counteracts for the developing energy deficit due to reduced mitochondrial function in the injured kidney.
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影响因子：
7.7
作者：
Domanski, Leszek;Safranow, Krzysztof;Ciechanowski, Kazimierz
通讯作者：
Ciechanowski, Kazimierz
DOI：
10.1016/b978-0-12-394309-5.00006-7
发表时间：
2012
影响因子：
--
作者：
Kalogeris, Theodore;Baines, Christopher P.;Krenz, Maike;Korthuis, Ronald J.
通讯作者：
Korthuis, Ronald J.
影响因子：
6.2
作者：
Damman, Jeffrey;Bloks, Vincent W.;Seelen, Marc A.
通讯作者：
Seelen, Marc A.
影响因子：
3.4
作者：
Levin, Yishai
通讯作者：
Levin, Yishai
影响因子：
3.7
作者：
Jouret F;Leenders J;Poma L;Defraigne JO;Krzesinski JM;de Tullio P
通讯作者：
de Tullio P