• 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

蛋白酶体是环境有毒有机锡的分子靶点。

The proteasome is a molecular target of environmental toxic organotins.

作者信息

Shi Guoqing, Chen Di, Zhai Guangshu, Chen Marina S, Cui Qiuzhi Cindy, Zhou Qunfang, He Bin, Dou Q Ping, Jiang Guibin

机构信息

State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, People's Republic of China.

出版信息

Environ Health Perspect. 2009 Mar;117(3):379-86. doi: 10.1289/ehp.11865. Epub 2008 Oct 23.

DOI:10.1289/ehp.11865
PMID:19337512
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2661907/
Abstract

BACKGROUND

Because of the vital importance of the proteasome pathway, chemicals affecting proteasome activity could disrupt essential cellular processes. Although the toxicity of organotins to both invertebrates and vertebrates is well known, the essential cellular target of organotins has not been well identified. We hypothesize that the proteasome is a molecular target of environmental toxic organotins.

OBJECTIVES

Our goal was to test the above hypothesis by investigating whether organotins could inhibit the activity of purified and cellular proteasomes and, if so, the involved molecular mechanisms and downstream events.

RESULTS

We found that some toxic organotins [e.g., triphenyltin (TPT)] can potently and preferentially inhibit the chymotrypsin-like activity of purified 20S proteasomes and human breast cancer cellular 26S proteasomes. Direct binding of tin atoms to cellular proteasomes is responsible for the observed irreversible inhibition. Inhibition of cellular proteasomes by TPT in several human cell lines results in the accumulation of ubiquitinated proteins and natural proteasome target proteins, accompanied by induction of cell death.

CONCLUSIONS

The proteasome is one of the molecular targets of environmental toxic organotins in human cells, and proteasome inhibition by organotins contributes to their cellular toxicity.

摘要

背景

由于蛋白酶体途径至关重要，影响蛋白酶体活性的化学物质可能会扰乱细胞的基本过程。尽管有机锡对无脊椎动物和脊椎动物的毒性众所周知，但其在细胞内的关键作用靶点尚未明确。我们推测蛋白酶体是环境中毒性有机锡的分子靶点。

目的

我们的目标是通过研究有机锡是否能抑制纯化的和细胞内蛋白酶体的活性，以及如果可以，其涉及的分子机制和下游事件，来验证上述假设。

结果

我们发现一些有毒有机锡[如三苯基锡（TPT）]能够有效且优先抑制纯化的20S蛋白酶体和人乳腺癌细胞26S蛋白酶体的类胰凝乳蛋白酶活性。锡原子与细胞内蛋白酶体的直接结合导致了观察到的不可逆抑制。TPT对多种人类细胞系中细胞蛋白酶体的抑制作用导致泛素化蛋白和天然蛋白酶体靶蛋白的积累，并伴随细胞死亡的诱导。

结论

蛋白酶体是人类细胞中环境中毒性有机锡的分子靶点之一，有机锡对蛋白酶体的抑制作用导致了它们的细胞毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bd7/2661907/4a68953d5e6c/ehp-117-379f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bd7/2661907/5b7936ab8936/ehp-117-379f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bd7/2661907/0e281dc176b3/ehp-117-379f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bd7/2661907/ff5e5ed4629e/ehp-117-379f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bd7/2661907/267c9523d5dd/ehp-117-379f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bd7/2661907/61d908e19474/ehp-117-379f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bd7/2661907/f7d38284b104/ehp-117-379f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bd7/2661907/4a68953d5e6c/ehp-117-379f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bd7/2661907/5b7936ab8936/ehp-117-379f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bd7/2661907/0e281dc176b3/ehp-117-379f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bd7/2661907/ff5e5ed4629e/ehp-117-379f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bd7/2661907/267c9523d5dd/ehp-117-379f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bd7/2661907/61d908e19474/ehp-117-379f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bd7/2661907/f7d38284b104/ehp-117-379f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1bd7/2661907/4a68953d5e6c/ehp-117-379f7.jpg

相似文献

1
The proteasome is a molecular target of environmental toxic organotins.蛋白酶体是环境有毒有机锡的分子靶点。
Environ Health Perspect. 2009 Mar;117(3):379-86. doi: 10.1289/ehp.11865. Epub 2008 Oct 23.
2
Molecular mechanisms of environmental organotin toxicity in mammals.哺乳动物环境有机锡毒性的分子机制。
Biol Pharm Bull. 2012;35(11):1876-80. doi: 10.1248/bpb.b212017.
3
Human exposure, biomarkers, and fate of organotins in the environment.人类暴露、生物标志物与环境中有机锡的归宿。
Rev Environ Contam Toxicol. 2011;213:27-54. doi: 10.1007/978-1-4419-9860-6_2.
4
Inhibition of proteasome activity by the dietary flavonoid apigenin is associated with growth inhibition in cultured breast cancer cells and xenografts.膳食类黄酮芹菜素对蛋白酶体活性的抑制作用与培养的乳腺癌细胞及异种移植瘤的生长抑制相关。
Breast Cancer Res. 2007;9(6):R80. doi: 10.1186/bcr1797.
5
Endocrine disruption induced by organotin compounds; organotins function as a powerful agonist for nuclear receptors rather than an aromatase inhibitor.有机锡化合物引起的内分泌干扰；有机锡作为核受体的强效激动剂而非芳香化酶抑制剂发挥作用。
J Toxicol Sci. 2008 Aug;33(3):269-76. doi: 10.2131/jts.33.269.
6
Inhibition of tumor proteasome activity by gold-dithiocarbamato complexes via both redox-dependent and -independent processes.金-二硫代氨基甲酸盐复合物通过氧化还原依赖和非依赖两种过程抑制肿瘤蛋白酶体活性。
J Cell Biochem. 2010 Jan 1;109(1):162-172. doi: 10.1002/jcb.22394.
7
Oncogenic addiction to high 26S proteasome level.致癌性对高 26S 蛋白酶体水平的成瘾性。
Cell Death Dis. 2018 Jul 10;9(7):773. doi: 10.1038/s41419-018-0806-4.
8
The human 26S proteasome is a target of antiretroviral agents.人类26S蛋白酶体是抗逆转录病毒药物的作用靶点。
AIDS. 2002 Mar 29;16(5):693-700. doi: 10.1097/00002030-200203290-00004.
9
Functional characterization of retinoid X receptor with an emphasis on the mediation of organotin poisoning in the Pacific oyster (Crassostrea gigas).视黄酸 X 受体功能特征研究——以太平洋牡蛎（Crassostrea gigas）中有机锡中毒的介导作用为例。
Gene. 2020 Aug 30;753:144780. doi: 10.1016/j.gene.2020.144780. Epub 2020 May 18.
10
Toxicity of organotin compounds: shared and unshared biochemical targets and mechanisms in animal cells.有机锡化合物的毒性：动物细胞中共同和非共同的生化靶标和机制。
Toxicol In Vitro. 2013 Mar;27(2):978-90. doi: 10.1016/j.tiv.2012.12.002. Epub 2012 Dec 8.

引用本文的文献

1
Neurodegenerative Proteinopathies Induced by Environmental Pollutants: Heat Shock Proteins and Proteasome as Promising Therapeutic Tools.环境污染物诱导的神经退行性蛋白质病：热休克蛋白和蛋白酶体作为有前景的治疗工具
Pharmaceutics. 2023 Jul 30;15(8):2048. doi: 10.3390/pharmaceutics15082048.
2
Toxicant-mediated redox control of proteostasis in neurodegeneration.神经退行性变中有毒物质介导的蛋白质稳态氧化还原调控
Curr Opin Toxicol. 2019 Feb;13:22-34. doi: 10.1016/j.cotox.2018.12.007. Epub 2018 Dec 28.
3
Proteasome-associated cysteine deubiquitinases are molecular targets of environmental optical brightener compounds.

本文引用的文献

1
Accumulation of organotin compounds in tissues and organs of stranded whales along the coasts of Thailand.泰国沿海搁浅鲸鱼组织和器官中有机锡化合物的积累情况。
Arch Environ Contam Toxicol. 2007 Jul;53(1):119-25. doi: 10.1007/s00244-006-0128-x. Epub 2007 Feb 5.
2
Apoptotic related biochemical changes in human amnion cells induced by tributyltin.三丁基锡诱导人羊膜细胞凋亡相关的生化变化
Toxicology. 2007 Jan 25;230(1):45-52. doi: 10.1016/j.tox.2006.10.026. Epub 2006 Dec 14.
3
Structure-proteasome-inhibitory activity relationships of dietary flavonoids in human cancer cells.
蛋白酶体相关半胱氨酸去泛素化酶是环境光增白剂化合物的分子靶标。
J Cell Biochem. 2019 Aug;120(8):14065-14075. doi: 10.1002/jcb.28682. Epub 2019 Apr 8.
4
Evaluating biological activity of compounds by transcription factor activity profiling.通过转录因子活性谱评估化合物的生物活性。
Sci Adv. 2018 Sep 26;4(9):eaar4666. doi: 10.1126/sciadv.aar4666. eCollection 2018 Sep.
5
Matrine inhibits prostate cancer via activation of the unfolded protein response/endoplasmic reticulum stress signaling and reversal of epithelial to mesenchymal transition.苦参碱通过激活未折叠蛋白反应/内质网应激信号通路和逆转上皮间质转化抑制前列腺癌。
Mol Med Rep. 2018 Jul;18(1):945-957. doi: 10.3892/mmr.2018.9061. Epub 2018 May 23.
6
Targeting the ubiquitin-proteasome system for cancer treatment: discovering novel inhibitors from nature and drug repurposing.以泛素-蛋白酶体系统为靶点进行癌症治疗：从天然产物中发现新型抑制剂及药物再利用。
Cancer Metastasis Rev. 2017 Dec;36(4):717-736. doi: 10.1007/s10555-017-9705-x.
7
Structural Consideration in Designing Organotin Polyethers to Arrest the Growth of Breast Cancer Cells In Vitro.设计有机锡聚醚以抑制体外乳腺癌细胞生长的结构考量
Materials (Basel). 2011 Apr 15;4(4):801-815. doi: 10.3390/ma4040801.
8
Np9, a cellular protein of retroviral ancestry restricted to human, chimpanzee and gorilla, binds and regulates ubiquitin ligase MDM2.Np9是一种起源于逆转录病毒的细胞蛋白，仅存在于人类、黑猩猩和大猩猩中，它能结合并调节泛素连接酶MDM2。
Cell Cycle. 2015;14(16):2619-33. doi: 10.1080/15384101.2015.1064565. Epub 2015 Jun 23.
9
Proteasome as a Molecular Target of Microcystin-LR.蛋白酶体作为微囊藻毒素-LR的分子靶点
Toxins (Basel). 2015 Jun 17;7(6):2221-31. doi: 10.3390/toxins7062221.
10
Turning tumor-promoting copper into an anti-cancer weapon via high-throughput chemistry.通过高通量化学将促进肿瘤的铜转化为抗癌武器。
Curr Med Chem. 2010;17(25):2685-98. doi: 10.2174/092986710791859315.
膳食类黄酮在人类癌细胞中的结构-蛋白酶体抑制活性关系
Front Biosci. 2007 Jan 1;12:1935-45. doi: 10.2741/2199.
4
In vitro metabolism of tributyltin and triphenyltin by human cytochrome P-450 isoforms.人细胞色素P-450同工酶对三丁基锡和三苯基锡的体外代谢
Toxicology. 2006 Dec 7;228(2-3):171-7. doi: 10.1016/j.tox.2006.08.023. Epub 2006 Aug 24.
5
Endocrine-disrupting organotin compounds are potent inducers of adipogenesis in vertebrates.内分泌干扰性有机锡化合物是脊椎动物脂肪生成的强效诱导剂。
Mol Endocrinol. 2006 Sep;20(9):2141-55. doi: 10.1210/me.2005-0367. Epub 2006 Apr 13.
6
Accumulation of organotin compounds and mercury in harbour porpoises (Phocoena phocoena) from the Danish waters and West Greenland.丹麦海域和西格陵兰岛港湾鼠海豚（Phocoena phocoena）体内有机锡化合物和汞的蓄积情况。
Sci Total Environ. 2005 Nov 1;350(1-3):59-71. doi: 10.1016/j.scitotenv.2005.02.038. Epub 2005 Apr 22.
7
Glutamate excitotoxicity is involved in cell death caused by tributyltin in cultured rat cortical neurons.谷氨酸兴奋性毒性参与了三丁基锡所致培养大鼠皮质神经元的细胞死亡。
Toxicol Sci. 2006 Jan;89(1):235-42. doi: 10.1093/toxsci/kfj007. Epub 2005 Oct 5.
8
O2 enhancement of human trophoblast differentiation and hCYP19 (aromatase) gene expression are mediated by proteasomal degradation of USF1 and USF2.氧气对人滋养层细胞分化和hCYP19（芳香化酶）基因表达的增强作用是由USF1和USF2的蛋白酶体降解介导的。
Mol Cell Biol. 2005 Oct;25(20):8824-33. doi: 10.1128/MCB.25.20.8824-8833.2005.
9
Apoptosis of cerebellar granule cells induced by organotin compounds found in drinking water: involvement of MAP kinases.饮用水中有机锡化合物诱导小脑颗粒细胞凋亡：丝裂原活化蛋白激酶的作用
Neurotoxicology. 2006 Jan;27(1):71-81. doi: 10.1016/j.neuro.2005.07.007. Epub 2005 Sep 21.
10
Dietary flavonoids as proteasome inhibitors and apoptosis inducers in human leukemia cells.膳食类黄酮作为人白血病细胞中的蛋白酶体抑制剂和凋亡诱导剂
Biochem Pharmacol. 2005 May 15;69(10):1421-32. doi: 10.1016/j.bcp.2005.02.022.