A Pilot Application of an iTRAQ-Based Proteomics Screen Estimates the Effects of Cigarette Smokers' Serum on RPE Cells With AMD High-Risk Alleles.
A Pilot Application of an iTRAQ-Based Proteomics Screen Estimates the Effects of Cigarette Smokers' Serum on RPE Cells With AMD High-Risk Alleles.
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基于 iTRAQ 的蛋白质组学筛选的试点应用评估了吸烟者血清对具有 AMD 高风险等位基因的 RPE 细胞的影响。
DOI：
10.1167/tvst.11.2.15
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发表时间：
2022-02-01
影响因子：
3
通讯作者：
Li X
中科院分区：
文献类型：
--
作者：
Cai B;Zhang Z;Sun S;Lin T;Ke Y;Li Z;Yang J;Li X
本研究旨在探讨遗传因素（ARMS 2/HTRA 1）和环境因素（吸烟）在老年性黄斑变性（AMD）发病中是否存在交互作用。原代人视网膜色素上皮（hRPE）细胞从具有AMD高危ARMS 2/HTRA 1等位基因的四个供体的眼睛获得，并且具有野生型等位基因的两个供体的眼睛用作对照。收集来自32名吸烟者和35名非吸烟者的合并血清，并分别用于处理hRPE细胞。使用基于相对和绝对定量（iTRAQ）的蛋白质组学的同量异序标签来鉴定相关蛋白质，并比较暴露于吸烟者血清后AMD高风险和低风险HTRA 1/ARMS 2等位基因之间的差异。在吸烟者血清刺激后，在高危等位基因细胞中检测到400个差异表达蛋白（DEP）。几种DEP参与神经元蛋白质变性和氧化应激途径。吸烟者血清刺激或HTRA 1过表达均可上调Caveolin-1表达，Caveolin-1是DEPs之一。此外，吸烟者血清还能增强体外培养的人RPE细胞的吞噬功能。研究证实AMD高危等位基因HTRA 1和吸烟可通过调节caveolin-1的表达促进AMD的发展。AMD高危等位基因和环境危险因素可通过调节小窝蛋白-1的表达促进AMD的发生和发展，其上调将在早期AMD病症中诱导响应于细胞应激的凋亡性细胞死亡。
The aim of this study was to explore whether there are interactions between genetic (ARMS2/HTRA1) and environmental factors (cigarette smoking) in the pathogenesis of age-related macular degeneration (AMD). Primary human retinal pigment epithelial (hRPE) cells were obtained from four donors’ eyes with AMD high-risk ARMS2/HTRA1 alleles, and two donors’ eyes with wild-type alleles were used as controls. The pooled serum from 32 smokers and 35 nonsmokers were collected and used separately to treat hRPE cells. The isobaric tag for relative and absolute quantitation (iTRAQ)-based proteomics was used to identify associated proteins and comparing the differences between AMD high-risk and low-risk HTRA1/ARMS2 alleles after exposure to smokers’ serum. After stimulation with the smokers’ serum, 400 differentially expressed proteins (DEPs) were detected in the high-risk allele cells. Several DEPs are involved in neuronal protein degeneration and oxidative stress pathways. The smokers’ serum stimulation or HTRA1 overexpression can both upregulate caveolin-1, which was one of the DEPs. Besides, the smokers’ serum enhanced the phagocytosis of cultured human RPE cells. The study confirmed the AMD high-risk alleles, HTRA1, and cigarette smoking can promote AMD development by regulating caveolin-1 expression. AMD high-risk alleles and environmental risk factors can promote the occurrence and development of AMD by regulating caveolin-1 expression, upregulation of which will induce apoptotic cell death in response to cellular stress in early AMD conditions.
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影响因子：
3.7
作者：
Fujihara, Masashi;Nagai, Norihiro;Sussan, Thomas E.;Biswal, Shyam;Handa, James T.
通讯作者：
Handa, James T.
香烟烟雾在培养的人视网膜色素上皮细胞中的生物学作用。
影响因子：
3.7
作者：
Yu AL;Birke K;Burger J;Welge-Lussen U
通讯作者：
Welge-Lussen U
影响因子：
3.3
作者：
Volonte, D;Zhang, K;Galbiati, F
通讯作者：
Galbiati, F
影响因子：
48
作者：
Wisniewski, Jacek R.;Zougman, Alexandre;Mann, Matthias
通讯作者：
Mann, Matthias
影响因子：
4.4
作者：
Tian, Jun;Yu, Wenzhen;Li, Xiaoxin
通讯作者：
Li, Xiaoxin