• 文献检索
  • 文档翻译
  • 深度研究
  • 学术资讯
  • Suppr Zotero 插件Zotero 插件
  • 邀请有礼
  • 套餐&价格
  • 历史记录
应用&插件
Suppr Zotero 插件Zotero 插件浏览器插件Mac 客户端Windows 客户端微信小程序
定价
高级版会员购买积分包购买API积分包
服务
文献检索文档翻译深度研究API 文档MCP 服务
关于我们
关于 Suppr公司介绍联系我们用户协议隐私条款
关注我们

Suppr 超能文献

核心技术专利：CN118964589B侵权必究
粤ICP备2023148730 号-1Suppr @ 2026

文献检索

告别复杂PubMed语法，用中文像聊天一样搜索，搜遍4000万医学文献。AI智能推荐，让科研检索更轻松。

立即免费搜索

文件翻译

保留排版，准确专业，支持PDF/Word/PPT等文件格式，支持 12+语言互译。

免费翻译文档

深度研究

AI帮你快速写综述，25分钟生成高质量综述，智能提取关键信息，辅助科研写作。

立即免费体验

氧化固醇处理诱导视网膜感光细胞系细胞活力丧失相关的转录组变化：一种史密斯-林利-奥皮茨综合征的体外模型。

Transcriptomic Changes Associated with Loss of Cell Viability Induced by Oxysterol Treatment of a Retinal Photoreceptor-Derived Cell Line: An In Vitro Model of Smith-Lemli-Opitz Syndrome.

机构信息

Department of Ophthalmology (Ross Eye Institute), Jacobs School of Medicine and Biomedical Sciences, SUNY-University at Buffalo, Buffalo, NY 14209, USA.

Research Service, VA Western NY Healthcare System, Buffalo, NY 14215, USA.

出版信息

Int J Mol Sci. 2021 Feb 26;22(5):2339. doi: 10.3390/ijms22052339.

DOI:10.3390/ijms22052339
PMID:33652836
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7956713/
Abstract

Smith-Lemli-Opitz Syndrome (SLOS) results from mutations in the gene encoding the enzyme DHCR7, which catalyzes conversion of 7-dehydrocholesterol (7DHC) to cholesterol (CHOL). Rats treated with a DHCR7 inhibitor serve as a SLOS animal model, and exhibit progressive photoreceptor-specific cell death, with accumulation of 7DHC and oxidized sterols. To understand the basis of this cell type specificity, we performed transcriptomic analyses on a photoreceptor-derived cell line (661W), treating cells with two 7DHC-derived oxysterols, which accumulate in tissues and bodily fluids of SLOS patients and in the rat SLOS model, as well as with CHOL (negative control), and evaluated differentially expressed genes (DEGs) for each treatment. Gene enrichment analysis and compilation of DEG sets indicated that endoplasmic reticulum stress, oxidative stress, DNA damage and repair, and autophagy were all highly up-regulated pathways in oxysterol-treated cells. Detailed analysis indicated that the two oxysterols exert their effects via different molecular mechanisms. Changes in expression of key genes in highlighted pathways (, , , and ) were validated by immunofluorescence confocal microscopy. The results extend our understanding of the pathobiology of retinal degeneration and SLOS, identifying potential new druggable targets for therapeutic intervention into these and other related orphan diseases.

摘要

Smith-Lemli-Opitz 综合征 (SLOS) 是由于编码酶 DHCR7 的基因突变引起的，该酶催化 7-脱氢胆固醇 (7DHC) 转化为胆固醇 (CHOL)。用 DHCR7 抑制剂处理的大鼠可作为 SLOS 动物模型，表现出进行性光感受器特异性细胞死亡，伴有 7DHC 和氧化固醇的积累。为了了解这种细胞类型特异性的基础，我们对光感受器衍生的细胞系 (661W) 进行了转录组分析，用两种在 SLOS 患者组织和体液中以及在大鼠 SLOS 模型中积累的 7DHC 衍生的氧化固醇以及 CHOL（阴性对照）处理细胞，并评估了每种处理的差异表达基因 (DEG)。基因富集分析和 DEG 集的汇编表明，内质网应激、氧化应激、DNA 损伤和修复以及自噬在氧化固醇处理的细胞中均高度上调。详细分析表明，两种氧化固醇通过不同的分子机制发挥作用。通过免疫荧光共聚焦显微镜验证了突出途径中关键基因 (,,, 和 ) 的表达变化。这些结果扩展了我们对视网膜变性和 SLOS 病理生物学的理解，为这些和其他相关孤儿疾病的治疗干预确定了潜在的新的可用药靶标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/a3f92ceeb4a9/ijms-22-02339-g019.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/c9b64dde163a/ijms-22-02339-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/2a1b6e395bb3/ijms-22-02339-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/bec09424b8b1/ijms-22-02339-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/51d348df5339/ijms-22-02339-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/50bf232eacb3/ijms-22-02339-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/e4e35c31ffce/ijms-22-02339-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/bacc81d6a29f/ijms-22-02339-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/bb06fff92df2/ijms-22-02339-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/913073bfd035/ijms-22-02339-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/77e1e8eaf09e/ijms-22-02339-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/f4e3181c4099/ijms-22-02339-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/cdca4e52afba/ijms-22-02339-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/2298a870a8c2/ijms-22-02339-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/074354edf307/ijms-22-02339-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/4549285bc4ef/ijms-22-02339-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/78e384888aeb/ijms-22-02339-g016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/b75ad756f89c/ijms-22-02339-g017.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/bac463542987/ijms-22-02339-g018.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/a3f92ceeb4a9/ijms-22-02339-g019.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/c9b64dde163a/ijms-22-02339-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/2a1b6e395bb3/ijms-22-02339-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/bec09424b8b1/ijms-22-02339-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/51d348df5339/ijms-22-02339-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/50bf232eacb3/ijms-22-02339-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/e4e35c31ffce/ijms-22-02339-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/bacc81d6a29f/ijms-22-02339-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/bb06fff92df2/ijms-22-02339-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/913073bfd035/ijms-22-02339-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/77e1e8eaf09e/ijms-22-02339-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/f4e3181c4099/ijms-22-02339-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/cdca4e52afba/ijms-22-02339-g012.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/2298a870a8c2/ijms-22-02339-g013.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/074354edf307/ijms-22-02339-g014.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/4549285bc4ef/ijms-22-02339-g015.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/78e384888aeb/ijms-22-02339-g016.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/b75ad756f89c/ijms-22-02339-g017.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/bac463542987/ijms-22-02339-g018.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/25a0/7956713/a3f92ceeb4a9/ijms-22-02339-g019.jpg

相似文献

1
Transcriptomic Changes Associated with Loss of Cell Viability Induced by Oxysterol Treatment of a Retinal Photoreceptor-Derived Cell Line: An In Vitro Model of Smith-Lemli-Opitz Syndrome.氧化固醇处理诱导视网膜感光细胞系细胞活力丧失相关的转录组变化：一种史密斯-林利-奥皮茨综合征的体外模型。
Int J Mol Sci. 2021 Feb 26;22(5):2339. doi: 10.3390/ijms22052339.
2
Oxysterols and Retinal Degeneration in a Rat Model of Smith-Lemli-Opitz Syndrome: Implications for an Improved Therapeutic Intervention.氧化固醇与 Smith-Lemli-Opitz 综合征大鼠模型中的视网膜变性：改善治疗干预的意义。
Molecules. 2018 Oct 22;23(10):2720. doi: 10.3390/molecules23102720.
3
Differential cytotoxic effects of 7-dehydrocholesterol-derived oxysterols on cultured retina-derived cells: Dependence on sterol structure, cell type, and density.7-脱氢胆固醇衍生的氧化甾醇对培养的视网膜衍生细胞的细胞毒性差异：取决于甾醇结构、细胞类型和密度。
Exp Eye Res. 2016 Apr;145:297-316. doi: 10.1016/j.exer.2016.01.016. Epub 2016 Feb 13.
4
Antioxidant supplementation ameliorates molecular deficits in Smith-Lemli-Opitz syndrome.抗氧化剂补充可改善 Smith-Lemli-Opitz 综合征的分子缺陷。
Biol Psychiatry. 2014 Feb 1;75(3):215-22. doi: 10.1016/j.biopsych.2013.06.013. Epub 2013 Jul 26.
5
Prevention of Retinal Degeneration in a Rat Model of Smith-Lemli-Opitz Syndrome.预防 Smith-Lemli-Opitz 综合征大鼠模型中的视网膜变性。
Sci Rep. 2018 Jan 19;8(1):1286. doi: 10.1038/s41598-018-19592-8.
6
7-Dehydrocholesterol-derived oxysterols and retinal degeneration in a rat model of Smith-Lemli-Opitz syndrome.史密斯-勒米-奥皮茨综合征大鼠模型中7-脱氢胆固醇衍生的氧化甾醇与视网膜变性
Biochim Biophys Acta. 2012 Jun;1821(6):877-83. doi: 10.1016/j.bbalip.2012.03.001. Epub 2012 Mar 9.
7
Light-induced exacerbation of retinal degeneration in a rat model of Smith-Lemli-Opitz syndrome.史密斯-莱姆利-奥皮茨综合征大鼠模型中光诱导的视网膜变性加重
Exp Eye Res. 2006 Mar;82(3):496-504. doi: 10.1016/j.exer.2005.08.008. Epub 2005 Dec 19.
8
Compromised phagosome maturation underlies RPE pathology in cell culture and whole animal models of Smith-Lemli-Opitz Syndrome.吞噬体成熟受损是 Smith-Lemli-Opitz 综合征细胞培养和整体动物模型中 RPE 病变的基础。
Autophagy. 2018;14(10):1796-1817. doi: 10.1080/15548627.2018.1490851. Epub 2018 Jul 31.
9
Biological activities of 7-dehydrocholesterol-derived oxysterols: implications for Smith-Lemli-Opitz syndrome.7-脱氢胆固醇衍生的氧化固醇的生物学活性：对 Smith-Lemli-Opitz 综合征的影响。
J Lipid Res. 2010 Nov;51(11):3259-69. doi: 10.1194/jlr.M009365. Epub 2010 Aug 11.
10
Retinal degeneration in a rat model of Smith-Lemli-Opitz Syndrome: thinking beyond cholesterol deficiency.Smith-Lemli-Opitz 综合征大鼠模型中的视网膜变性：超越胆固醇缺乏的思考。
Adv Exp Med Biol. 2010;664:481-9. doi: 10.1007/978-1-4419-1399-9_55.

引用本文的文献

1
Exploring Recent Developments in the Manifestation, Diagnosis, and Treatment of Patients with Smith-Lemli-Opitz Syndrome: From Molecular Pathways to Clinical Innovations.探索史密斯-勒米-奥皮茨综合征患者的临床表现、诊断和治疗的最新进展：从分子途径到临床创新
Int J Mol Sci. 2025 Jul 11;26(14):6672. doi: 10.3390/ijms26146672.
2
Hydroxyzine Effects on Post-Lanosterol Biosynthesis in Smith-Lemli-Opitz Syndrome (SLOS) Models.羟嗪对史密斯-勒米-奥皮茨综合征（SLOS）模型中羊毛甾醇生物合成后阶段的影响。
Biomolecules. 2025 Apr 10;15(4):562. doi: 10.3390/biom15040562.
3
Role of traditional Chinese medicine in age-related macular degeneration: exploring the gut microbiota's influence.

本文引用的文献

1
Photoreceptor Degeneration in Pro23His Transgenic Rats (Line 3) Involves Autophagic and Necroptotic Mechanisms.Pro23His转基因大鼠（第3系）中的光感受器退化涉及自噬和坏死性凋亡机制。
Front Neurosci. 2020 Nov 3;14:581579. doi: 10.3389/fnins.2020.581579. eCollection 2020.
2
Oxiapoptophagy: A type of cell death induced by some oxysterols.氧化凋亡噬作用：一种由某些氧化固醇诱导的细胞死亡方式。
Br J Pharmacol. 2021 Aug;178(16):3115-3123. doi: 10.1111/bph.15173. Epub 2020 Jul 23.
3
The PERK-Dependent Molecular Mechanisms as a Novel Therapeutic Target for Neurodegenerative Diseases.
中药在年龄相关性黄斑变性中的作用：探究肠道微生物群的影响。
Front Pharmacol. 2024 Jan 25;15:1356324. doi: 10.3389/fphar.2024.1356324. eCollection 2024.
4
Morphological, biochemical, and transcriptomic characterization of iPSC-derived human RPE cells from normal and Smith-Lemli-Opitz syndrome patients.来自正常和史密斯-勒米-奥皮茨综合征患者的诱导多能干细胞衍生的人视网膜色素上皮细胞的形态学、生化和转录组学特征
Mol Vis. 2022 Nov 12;28:394-411. eCollection 2022.
PERK 依赖性分子机制作为神经退行性疾病的新型治疗靶点。
Int J Mol Sci. 2020 Mar 19;21(6):2108. doi: 10.3390/ijms21062108.
4
mTOR may interact with PARP-1 to regulate visible light-induced parthanatos in photoreceptors.mTOR 可能与 PARP-1 相互作用，以调节光感受器中可见光诱导的 parthanatos。
Cell Commun Signal. 2020 Feb 17;18(1):27. doi: 10.1186/s12964-019-0498-0.
5
Autophagy as a Cellular Stress Response Mechanism in the Nervous System.自噬作为神经系统中的一种细胞应激反应机制。
J Mol Biol. 2020 Apr 3;432(8):2560-2588. doi: 10.1016/j.jmb.2020.01.017. Epub 2020 Jan 18.
6
Cell Cycle Proteins as Key Regulators of Postmitotic Cell Death.细胞周期蛋白作为有丝分裂后细胞死亡的关键调节因子。
Yale J Biol Med. 2019 Dec 20;92(4):641-650. eCollection 2019 Dec.
7
ER Stress Induces Cell Cycle Arrest at the G2/M Phase Through eIF2α Phosphorylation and GADD45α.内质网应激通过 eIF2α 磷酸化和 GADD45α 诱导细胞周期停滞在 G2/M 期。
Int J Mol Sci. 2019 Dec 13;20(24):6309. doi: 10.3390/ijms20246309.
8
PRAS40 suppresses atherogenesis through inhibition of mTORC1-dependent pro-inflammatory signaling in endothelial cells.Pras40 通过抑制内皮细胞中 mTORC1 依赖性促炎信号来抑制动脉粥样硬化形成。
Sci Rep. 2019 Nov 14;9(1):16787. doi: 10.1038/s41598-019-53098-1.
9
Systematic spatiotemporal mapping reveals divergent cell death pathways in three mouse models of hereditary retinal degeneration.系统的时空图谱揭示了遗传性视网膜变性三种小鼠模型中不同的细胞死亡途径。
J Comp Neurol. 2020 May;528(7):1113-1139. doi: 10.1002/cne.24807. Epub 2019 Nov 26.
10
Programmed Cell-Death by Ferroptosis: Antioxidants as Mitigators.铁死亡程序性细胞死亡：抗氧化剂作为缓解剂。
Int J Mol Sci. 2019 Oct 8;20(19):4968. doi: 10.3390/ijms20194968.