USP48 deubiquitination stabilizes SLC1A5 to inhibit retinal pigment epithelium cell inflammation, oxidative stress and ferroptosis in the progression of diabetic retinopathy.

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS
ACS Applied Bio Materials Pub Date : 2024-06-01 Epub Date: 2024-03-01 DOI:10.1007/s10863-024-10008-z
Guoping Zhang, Jinsong Yu, Youping Wan
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引用次数: 0

Abstract

Background: Diabetic retinopathy is one of the complications of diabetes mellitus. The aim of this study was to explore the effects of ubiquitin-specific protease 48 (USP48) and its underlying mechanisms in the development of diabetic retinopathy.

Methods: CCK-8 assay, EdU assay, and flow cytometry were used to measure the proliferative ability and the apoptotic rate of ARPE-19 cells, respectively. ELISA kits were utilized to assess the levels of inflammatory cytokines. The levels of Fe2+, ROS and MDA were detected using the corresponding biochemical kits. The protein expression of USP48 and SLC1A5 was examined through western blot. The mRNA level of SLC1A5 was determined using RT-qPCR. The interaction relationship between USP48 and SLC1A5 was evaluated using Co-IP assay.

Results: High glucose (HG) treatment significantly inhibited cell proliferation and elevated cell apoptosis, inflammation, ferroptosis and oxidative stress in ARPE-19 cells. HG treatment-caused cell damage was hindered by USP48 or SLC1A5 overexpression in ARPE-19 cells. Fer-1 treatment improved HG-caused cell damage in ARPE-19 cells, which was blocked by USP48 knockdown. Moreover, USP48 knockdown decreased SLC1A5 expression. SLC1A5 downregulation reversed the improvement effects of USP48 upregulation on cell damage in HG-treated ARPE-19 cells.

Conclusion: USP48 overexpression deubiquitinated SLC1A5 to elevate cell proliferation and suppress cell apoptosis, inflammation, ferroptosis and oxidative stress in HG-triggered ARPE-19 cells, thereby inhibiting the progression of diabetic retinopathy.

Abstract Image

USP48 去泛素化能稳定 SLC1A5,从而在糖尿病视网膜病变进展过程中抑制视网膜色素上皮细胞炎症、氧化应激和铁蛋白沉着。
背景:糖尿病视网膜病变是糖尿病并发症之一:糖尿病视网膜病变是糖尿病并发症之一。本研究旨在探讨泛素特异性蛋白酶 48(USP48)在糖尿病视网膜病变发展过程中的作用及其内在机制:方法:使用 CCK-8 检测法、EdU 检测法和流式细胞术分别测量 ARPE-19 细胞的增殖能力和凋亡率。利用 ELISA 试剂盒评估炎症细胞因子的水平。使用相应的生化试剂盒检测 Fe2+、ROS 和 MDA 的水平。USP48 和 SLC1A5 的蛋白表达通过 Western 印迹进行检测。使用 RT-qPCR 检测 SLC1A5 的 mRNA 水平。通过 Co-IP 分析评估了 USP48 和 SLC1A5 之间的相互作用关系:结果:高糖(HG)处理明显抑制了 ARPE-19 细胞的增殖,并增加了细胞凋亡、炎症、铁变态反应和氧化应激。在 ARPE-19 细胞中,USP48 或 SLC1A5 的过表达阻碍了 HG 处理引起的细胞损伤。Fer-1 处理可改善 HG 在 ARPE-19 细胞中引起的细胞损伤,而 USP48 敲除可阻止这种损伤。此外,USP48 基因敲除会降低 SLC1A5 的表达。SLC1A5 下调逆转了 USP48 上调对 HG 处理的 ARPE-19 细胞损伤的改善作用:结论:USP48 的过表达能使 SLC1A5 去泛素化,从而促进细胞增殖,抑制 HG 触发的 ARPE-19 细胞的细胞凋亡、炎症、铁中毒和氧化应激,从而抑制糖尿病视网膜病变的进展。
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来源期刊
ACS Applied Bio Materials
ACS Applied Bio Materials Chemistry-Chemistry (all)
CiteScore
9.40
自引率
2.10%
发文量
464
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