Redox phospholipidomics analysis reveals specific oxidized phospholipids and regions in the diabetic mouse kidney.
Redox phospholipidomics analysis reveals specific oxidized phospholipids and regions in the diabetic mouse kidney.
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DOI：
10.1016/j.redox.2022.102520
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发表时间：
2022-12
期刊：
影响因子：
11.4
通讯作者：
Stadler, Krisztian
中科院分区：
文献类型：
--
作者：
McCrimmon, Allison;Corbin, Sydney;Shrestha, Bindesh;Roman, Gregory;Dhungana, Suraj;Stadler, Krisztian
关键词：
虽然人们普遍认为氧化应激会影响糖尿病肾脏并导致发病，但对各种反应性物质的分子实体和解剖位置的了解还相当缺乏。在这里，我们提供了一个新的“氧化应激地图”的糖尿病肾脏-第一种，并确定具体的，氧化和其他反应性脂质及其位置。我们使用db/db小鼠模型和解吸电喷雾电离（DESI）质谱结合热图图像分析。我们使用DESI成像分析了正常（db/m）和糖尿病（db/db）肾脏中磷脂过氧化物的全面阵列。生成肾脏的氧化脂质组学热图，重点关注磷脂及其潜在的过氧化产物。我们确定了在糖尿病肾病中发生过氧化反应的脂质。几种磷脂过氧化物及其空间分布被确定为糖尿病肾脏特有的，在氧化磷脂酰乙醇胺（PE）和溶血磷脂酰乙醇胺显着富集。除了关于目标的定性和半定量信息之外，该方法还揭示了脂质过氧化物信号在肾脏中传播的解剖位置和程度。我们的方法提供了新的，深入的信息的位置和分子实体的反应性脂质在一个器官具有非常异质的景观。这些反应性脂质中的许多先前已与程序性细胞死亡机制相关联。因此，这些发现可能有助于了解磷脂过氧化对糖尿病肾病中细胞和线粒体膜完整性以及氧化还原脂质信号传导的影响。氧化应激是糖尿病肾病发病的主要因素之一。在这里，使用一种创新的质谱方法（DESI），我们提供了一种新的糖尿病肾脏的氧化脂质组学图谱。我们的分析显示，在糖尿病肾脏的特定区域富集特定的含氧磷脂物质。我们的发现可能会进一步加深我们对脂质过氧化作用如何以及在何处影响糖尿病肾脏的理解。
While it is generally accepted that oxidative stress impacts the diabetic kidney and contributes to pathogenesis, there is a substantial lack of knowledge about the molecular entity and anatomic location of a variety of reactive species. Here we provide a novel “oxidative stress map” of the diabetic kidney – the first of its kind, and identify specific, oxidized and other reactive lipids and their location. We used the db/db mouse model and Desorption Electrospray Ionization (DESI) mass spectrometry combined with heatmap image analysis. We analyzed a comprehensive array of phospholipid peroxide species in normal (db/m) and diabetic (db/db) kidneys using DESI imaging. Oxilipidomics heatmaps of the kidneys were generated focusing on phospholipids and their potential peroxidized products. We identified those lipids that undergo peroxidation in diabetic nephropathy. Several phospholipid peroxides and their spatial distribution were identified that were specific to the diabetic kidney, with significant enrichment in oxygenated phosphatidylethanolamines (PE) and lysophosphatidylethanolamine. Beyond qualitative and semi-quantitative information about the targets, the approach also reveals the anatomic location and the extent of lipid peroxide signal propagation across the kidney. Our approach provides novel, in-depth information of the location and molecular entity of reactive lipids in an organ with a very heterogeneous landscape. Many of these reactive lipids have been previously linked to programmed cell death mechanisms. Thus, the findings may be relevant to understand what impact phospholipid peroxidation has on cell and mitochondria membrane integrity and redox lipid signaling in diabetic nephropathy. Oxidative stress is one of the major players in the pathogenesis of diabetic nephropathy. Here, using an innovative mass spectrometry approach (DESI), we provide a novel oxilipidomics map of the diabetic kidney. Our analysis revealed enrichment of specific oxygenated phospholipid species at specific regions of the diabetic kidney. Our findings will likely further our understanding in how and where lipid peroxidation impacts the diabetic kidney.
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DOI：
10.3109/10715769209061085
发表时间：
1992-01-01
期刊：
FREE RADICAL RESEARCH COMMUNICATIONS
影响因子：
--
作者：
DARLEYUSMAR, VM;HOGG, N;MONCADA, S
通讯作者：
MONCADA, S
影响因子：
21.3
作者：
Friedmann Angeli JP;Schneider M;Proneth B;Tyurina YY;Tyurin VA;Hammond VJ;Herbach N;Aichler M;Walch A;Eggenhofer E;Basavarajappa D;Rådmark O;Kobayashi S;Seibt T;Beck H;Neff F;Esposito I;Wanke R;Förster H;Yefremova O;Heinrichmeyer M;Bornkamm GW;Geissler EK;Thomas SB;Stockwell BR;O'Donnell VB;Kagan VE;Schick JA;Conrad M
通讯作者：
Conrad M
影响因子：
4.6
作者：
Escribano-Lopez I;Diaz-Morales N;Iannantuoni F;Lopez-Domenech S;de Marañon AM;Abad-Jimenez Z;Bañuls C;Rovira-Llopis S;Herance JR;Rocha M;Victor VM
通讯作者：
Victor VM
影响因子：
64.8
作者：
Chouchani ET;Kazak L;Jedrychowski MP;Lu GZ;Erickson BK;Szpyt J;Pierce KA;Laznik-Bogoslavski D;Vetrivelan R;Clish CB;Robinson AJ;Gygi SP;Spiegelman BM
通讯作者：
Spiegelman BM
影响因子：
6.5
作者：
Grove, Kerri J.;Voziyan, Paul A.;Caprioli, Richard M.
通讯作者：
Caprioli, Richard M.