Proteomic Analysis of Retinal Mitochondria-Associated ER Membranes Identified Novel Proteins of Retinal Degeneration in Long-Term Diabetes.
Proteomic Analysis of Retinal Mitochondria-Associated ER Membranes Identified Novel Proteins of Retinal Degeneration in Long-Term Diabetes.
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DOI：
10.3390/cells11182819
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发表时间：
2022-09-09
期刊：
影响因子：
6
通讯作者：
Zhang, Sarah X.
中科院分区：
文献类型：
--
作者：
Wang, Joshua J.;Park, Karen Sophia;Dhimal, Narayan;Shen, Shichen;Tang, Xixiang;Qu, Jun;Zhang, Sarah X.
关键词：
线粒体相关的内质网（ER）膜（MAM）是ER和线粒体之间的物理接触部位，在钙信号传导、生物能量学和炎症的调节中起着至关重要的作用。这些过程的紊乱以及ER和线粒体稳态的失调有助于糖尿病视网膜病变（DR）的发病机制。然而，很少有研究探讨糖尿病对视网膜MAM的影响及其在DR发病机制中的意义。在本研究中，我们研究了长埃文斯大鼠与链脲佐菌素诱导的长期1型糖尿病视网膜MAM的蛋白质组学变化。此外，我们进行了深入的生物信息学分析，以确定可能与视网膜炎症，血管生成和神经变性有关的关键MAM蛋白和途径。采用IonStar蛋白质组学流水线技术对大鼠视网膜MAM中2664个独特蛋白质进行定量分析，其中179个蛋白质在糖尿病中发生了显著变化。功能注释显示，这179种蛋白质参与重要的生物学过程，如细胞存活、炎症反应和细胞维持，以及多种疾病相关的信号通路，例如，整联蛋白信号传导、白细胞外渗、PPAR、PTEN和RhoGDI信号传导。本研究为糖尿病视网膜MAM蛋白的变化提供了全面的信息，有助于了解DR代谢功能障碍和视网膜细胞损伤的机制。
The mitochondria-associated endoplasmic reticulum (ER) membrane (MAM) is the physical contact site between the ER and the mitochondria and plays a vital role in the regulation of calcium signaling, bioenergetics, and inflammation. Disturbances in these processes and dysregulation of the ER and mitochondrial homeostasis contribute to the pathogenesis of diabetic retinopathy (DR). However, few studies have examined the impact of diabetes on the retinal MAM and its implication in DR pathogenesis. In the present study, we investigated the proteomic changes in retinal MAM from Long Evans rats with streptozotocin-induced long-term Type 1 diabetes. Furthermore, we performed in-depth bioinformatic analysis to identify key MAM proteins and pathways that are potentially implicated in retinal inflammation, angiogenesis, and neurodegeneration. A total of 2664 unique proteins were quantified using IonStar proteomics-pipeline in rat retinal MAM, among which 179 proteins showed significant changes in diabetes. Functional annotation revealed that the 179 proteins are involved in important biological processes such as cell survival, inflammatory response, and cellular maintenance, as well as multiple disease-relevant signaling pathways, e.g., integrin signaling, leukocyte extravasation, PPAR, PTEN, and RhoGDI signaling. Our study provides comprehensive information on MAM protein changes in diabetic retinas, which is helpful for understanding the mechanisms of metabolic dysfunction and retinal cell injury in DR.
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影响因子：
4.4
作者：
Jadeja S;Mort RL;Keighren M;Hart AW;Joynson R;Wells S;Potter PK;Jackson IJ
通讯作者：
Jackson IJ
影响因子：
15.9
作者：
Barber, AJ;Lieth, E;Gardner, TW
通讯作者：
Gardner, TW
DOI：
10.1007/s00417-017-3679-9
发表时间：
2017-08
期刊：
Graefe's archive for clinical and experimental ophthalmology = Albrecht von Graefes Archiv fur klinische und experimentelle Ophthalmologie
影响因子：
--
作者：
Al-Khersan H;Shah KP;Jung SC;Rodriguez A;Madduri RK;Grassi MA
通讯作者：
Grassi MA
内质网应激与视网膜炎症和糖尿病性视网膜病有关。
影响因子：
3.5
作者：
Li, Jingming;Wang, Joshua J.;Yu, Qiang;Wang, Min;Zhang, Sarah X.
通讯作者：
Zhang, Sarah X.
影响因子：
4.8
作者：
Huang, Chuangxin;Wang, Joshua J.;Zhang, Sarah X.
通讯作者：
Zhang, Sarah X.