Association of Impaired Reactive Aldehyde Metabolism with Delayed Graft Function in Human Kidney Transplantation.
Association of Impaired Reactive Aldehyde Metabolism with Delayed Graft Function in Human Kidney Transplantation.
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人肾移植中反应性醛代谢受损与移植物功能延迟的关系。
DOI：
10.1155/2018/3704129
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发表时间：
2018
影响因子：
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通讯作者：
Gross,EricR
中科院分区：
文献类型：
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作者：
Wijermars,LeonieGM;Schaapherder,AlexanderF;George,Thomas;Sinharoy,Pritam;Gross,EricR
移植肾功能延迟是肾移植后的早期并发症，其分子机制尚不清楚。在这里，我们确定反应醛代谢受损是否与移植肾功能延迟有关。通过独创性基因通路分析，对移植物功能延迟的人肾活检组织和未发生移植物功能延迟的移植物进行了比较。通过检测反应醛代谢、反应醛诱导的蛋白加合物形成以及乙醛脱氢酶(ALDH)基因和蛋白的表达，比较第二组移植物功能延迟的移植物(n=10)和未发生移植物功能延迟的移植物(n=10)。在第一系列肾脏活检中，几个已知代谢反应性醛的基因家族，如醛脱氢酶(ALDH)、醛酮还原酶(AKR)和谷胱甘肽-S转移酶(GSTA)，在没有发生移植功能延迟的肾脏中上调。在第二个系列的移植肾中，我们重点检测了乙醛诱导的蛋白加合物和ALDH酶活性。在移植肾功能延迟的肾脏中，ALDH酶的反应性醛代谢减少(分别为37 ± 12∗比79 ± 5μg/μ/mg组织，∗P<；0.005)。ALDH酶活性与肾移植后住院时间呈负相关。总而言之，我们的研究发现，与没有发生移植功能延迟的肾脏相比，ALDH酶活性降低。ALDH酶活性和反应性醛诱导蛋白加合物的测定有可能被进一步开发为评估移植肾功能延迟和肾移植恢复的生物标志物。
Delayed graft function is an early complication following kidney transplantation with an unclear molecular mechanism. Here we determined whether impaired reactive aldehyde metabolism is associated with delayed graft function. Human kidney biopsies from grafts with delayed graft function were compared with grafts that did not develop delayed graft function by Ingenuity gene pathway analysis. A second series of grafts with delayed graft function (n= 10) were compared to grafts that did not develop delayed graft function (n= 10) by measuring reactive aldehyde metabolism, reactive aldehyde‐induced protein adduct formation, and aldehyde dehydrogenase (ALDH) gene and protein expression. In the first series of kidney biopsies, several gene families known for metabolizing reactive aldehydes, such as aldehyde dehydrogenase (ALDH), aldo‐keto reductase (AKR), and glutathione‐S transferase (GSTA), were upregulated in kidneys that did not develop delayed graft function versus those that did. In the second series of kidney grafts, we focused on measuring aldehyde‐induced protein adducts and ALDH enzymatic activity. The reactive aldehyde metabolism by ALDH enzymes was reduced in kidneys with delayed graft function compared to those that did not (37 ± 12∗vs. 79 ± 5μg/min/mg tissue,∗P< 0.005, respectively). ALDH enzymatic activity was also negatively correlated with length of hospital stay after a kidney transplant. Together, our study identifies a reduced ALDH enzymatic activity with kidneys developing delayed graft function compared to those that did not. Measuring ALDH enzymatic activity and reactive aldehyde‐induced protein adducts can potentially be further developed as a biomarker to assess for delayed graft function and recovery from a kidney transplant.