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Tissue metabolic profiling shows that saccharopine accumulates during renal ischemic-reperfusion injury, while kynurenine and itaconate accumulate in renal allograft rejection.
Metabolomics ( IF 3.6 ) Pub Date : 2020-05-04 , DOI: 10.1007/s11306-020-01682-2
Ulf H Beier 1 , Erum A Hartung 1 , Seth Concors 2 , Paul T Hernandez 2 , Zhonglin Wang 2 , Caroline Perry 3 , Joseph A Baur 3 , Michelle R Denburg 1 , Wayne W Hancock 4 , Terence P Gade 5, 6 , Matthew H Levine 2
Affiliation  

To examine metabolic differences between renal allograft acute cellular rejection (ACR) and ischemic-reperfusion injury (IRI), we transplanted MHC-mismatched kidneys and induced 28 min warm-IRI, and collected the ACR and IRI kidneys as well as their respective native and collateral control kidneys. We extracted metabolites from the kidney tissues and found the lysine catabolite saccharopine 12.5-fold enriched in IRI kidneys, as well as the immunometabolites itaconate and kynurenine in ACR kidneys. Saccharopine accumulation is known to be toxic to mitochondria and may contribute to IRI pathophysiology, while itaconate and kynurenine may be reflective of counterregulatory responses to immune activation in ACR.

中文翻译:

组织代谢分析表明,糖精在肾缺血-再灌注损伤中蓄积,而犬尿氨酸和衣康酸酯在同种异体肾移植排斥反应中蓄积。

为了检查肾同种异体移植急性细胞排斥反应(ACR)与缺血再灌注损伤(IRI)之间的代谢差异,我们移植了MHC不匹配的肾脏并诱导了28分钟的温暖IRI,并收集了ACR和IRI肾脏以及它们各自的天然肾间接控制肾脏。我们从肾脏组织中提取了代谢物,发现IRI肾脏中的赖氨酸分解代谢物saccharopine富集12.5倍,ACR肾脏中的衣康酸酯和犬尿氨酸为免疫代谢产物。糖精积累对线粒体有毒,可能有助于IRI病理生理,而衣康酸酯和犬尿氨酸可能反映了ACR对免疫激活的反调节反应。
更新日期:2020-05-04
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