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Diabetic nephropathy associates with deregulation of enzymes involved in kidney sulphur metabolism.
Journal of Cellular and Molecular Medicine ( IF 4.3 ) Pub Date : 2020-09-16 , DOI: 10.1111/jcmm.15855
Elena Uyy 1 , Viorel Iulian Suica 1 , Raluca Maria Boteanu 1 , Florentina Safciuc 1 , Aurel Cerveanu-Hogas 1 , Luminita Ivan 1 , Crina Stavaru 2 , Maya Simionescu 1 , Felicia Antohe 1
Affiliation  

Nephropathy is a major chronic complication of diabetes. A crucial role in renal pathophysiology is played by hydrogen sulphide (H2S) that is produced excessively by the kidney; however, the data regarding H2S bioavailability are inconsistent. We hypothesize that early type 1 diabetes (T1D) increases H2S production by a mechanism involving hyperglycaemia‐induced alterations in sulphur metabolism. Plasma and kidney tissue collected from T1D double transgenic mice were subjected to mass spectrometry‐based proteomic analysis, and the results were validated by immunological and gene expression assays.T1D mice exhibited a high concentration of H2S in the plasma and kidney tissue and histological, showed signs of subtle kidney fibrosis, characteristic for early renal disease. The shotgun proteomic analyses disclosed that the level of enzymes implicated in sulphate activation modulators, H2S‐oxidation and H2S‐production were significantly affected (ie 6 up‐regulated and 4 down‐regulated). Gene expression results corroborated well with the proteomic data. Dysregulation of H2S enzymes underly the changes occurring in H2S production, which in turn could play a key role in the initiation of renal disease. The new findings lead to a novel target in the therapy of diabetic nephropathy. Mass spectrometry data are available via ProteomeXchange with identifier PXD018053.

中文翻译:

糖尿病性肾病与参与肾脏硫代谢的酶的失调有关。

肾病是糖尿病的主要慢性并发症。肾脏过度产生的硫化氢(H 2 S)在肾脏病理生理中起着至关重要的作用。但是,有关H 2 S生物利用度的数据不一致。我们假设早期1型糖尿病(T1D)通过一种涉及高血糖引起的硫代谢改变的机制来增加H 2 S的产生。从T1D双转基因小鼠中收集的血浆和肾脏组织进行了基于质谱的蛋白质组学分析,并通过免疫学和基因表达分析验证了结果.T1D小鼠表现出高浓度的H 2S在血浆和肾脏组织及组织学中,表现出细微的肾脏纤维化的迹象,这是早期肾脏疾病的特征。shot弹枪蛋白质组学分析表明,硫酸盐活化调节剂,H 2 S氧化H 2 S产生中涉及的酶水平受到显着影响(即6个上调和4个下调)。基因表达结果与蛋白质组学数据得到了很好的证实。H的失调2小号酶underly H中发生的变化2S的产生反过来可能在肾病的发生中起关键作用。新发现导致糖尿病肾病治疗的新目标。质谱数据可通过ProteomeXchange获得,其标识符为PXD018053。
更新日期:2020-10-22
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