• 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

甲素对CCL2/MCP-1的蛋白水解加工及失活作用

Proteolytic processing and inactivation of CCL2/MCP-1 by meprins.

作者信息

Herzog Christian, Haun Randy S, Shah Sudhir V, Kaushal Gur P

机构信息

Central Arkansas Veterans Healthcare System, Little Rock, AR, USA.

University of Arkansas for Medical Sciences, Department of Internal Medicine, Little Rock, AR, USA.

出版信息

Biochem Biophys Rep. 2016 Aug 21;8:146-150. doi: 10.1016/j.bbrep.2016.08.019. eCollection 2016 Dec.

DOI:10.1016/j.bbrep.2016.08.019
PMID:28955950
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5613766/
Abstract

Monocyte chemotactic protein 1 (CCL2/MCP-1) is a small chemokine involved in the recruitment and trafficking of mononuclear immune cells to inflammation sites. Our studies demonstrate that the metalloendopeptidases meprin A (purified from kidney cortex), recombinant meprin α, and recombinant meprin β can all process CCL2/MCP-1. The cleavage sites were determined by amino acid sequencing and mass spectrometry analysis of the generated products, and the biological activity of the products was evaluated by chemotactic migration assay using THP-1 cells. The cleavage sites generated by the meprin isoforms revealed that meprin A and meprin α cleaved the N-terminal domain of mouse CCL2/MCP-1 at the Asn and Ala bond, resulting in significant reduction in the chemotactic activity of the cleaved CCL2/MCP-1. Meprin β was unable to cleave the N-terminus of mouse CCL2/MCP-1 but cleaved the C-terminal region between Ser and Glu. Human CCL2/MCP-1 that lacks the murine C-terminal region was also cleaved by meprin α at the N-terminus resulting in significant loss of CCL2/MCP-1 biological activity, whereas meprin β did not affect the biological activity. These studies suggest that meprin α and meprin β may play important roles in regulating the CCL2/MCP-1 chemokine activity during inflammation.

摘要

单核细胞趋化蛋白1（CCL2/MCP-1）是一种小分子趋化因子，参与单核免疫细胞向炎症部位的募集和运输。我们的研究表明，金属内肽酶meprin A（从肾皮质纯化）、重组meprinα和重组meprinβ都可以加工CCL2/MCP-1。通过对生成产物的氨基酸测序和质谱分析确定切割位点，并使用THP-1细胞通过趋化迁移试验评估产物的生物活性。meprin同工型产生的切割位点表明，meprin A和meprinα在Asn和Ala键处切割小鼠CCL2/MCP-1的N端结构域，导致切割后的CCL2/MCP-activity的趋化活性显著降低。Meprinβ无法切割小鼠CCL2/MCP-1的N端，但能切割Ser和Glu之间的C端区域。缺乏鼠C端区域的人CCL2/MCP-1也被meprinα在N端切割，导致CCL2/MCP-1生物活性显著丧失，而meprinβ不影响生物活性。这些研究表明，meprinα和meprinβ可能在炎症过程中调节CCL2/MCP-1趋化因子活性方面发挥重要作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/5613766/737b2b4a037b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/5613766/abfa5379a75d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/5613766/c091cec368aa/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/5613766/89040d7243fb/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/5613766/737b2b4a037b/gr4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/5613766/abfa5379a75d/gr1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/5613766/c091cec368aa/gr2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/5613766/89040d7243fb/gr3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/deb6/5613766/737b2b4a037b/gr4.jpg

相似文献

1
Proteolytic processing and inactivation of CCL2/MCP-1 by meprins.甲素对CCL2/MCP-1的蛋白水解加工及失活作用
Biochem Biophys Rep. 2016 Aug 21;8:146-150. doi: 10.1016/j.bbrep.2016.08.019. eCollection 2016 Dec.
2
Isoform-specific interactions between meprin metalloproteases and the catalytic subunit of protein kinase A: significance in acute and chronic kidney injury.金属蛋白酶 meprin 同工型与蛋白激酶 A 催化亚基的同工型特异性相互作用：在急性和慢性肾损伤中的意义。
Am J Physiol Renal Physiol. 2015 Jan 1;308(1):F56-68. doi: 10.1152/ajprenal.00167.2014. Epub 2014 Oct 29.
3
Role of meprin metalloproteinases in cytokine processing and inflammation.金属蛋白酶 meprin 在细胞因子加工和炎症中的作用。
Cytokine. 2019 Feb;114:18-25. doi: 10.1016/j.cyto.2018.11.032. Epub 2018 Dec 20.
4
Maturation of secreted meprin alpha during biosynthesis: role of the furin site and identification of the COOH-terminal amino acids of the mouse kidney metalloprotease subunit.生物合成过程中分泌型金属蛋白酶α的成熟：弗林蛋白酶切割位点的作用及小鼠肾脏金属蛋白酶亚基羧基末端氨基酸的鉴定
Arch Biochem Biophys. 1998 Jan 1;349(1):192-200. doi: 10.1006/abbi.1997.0453.
5
Villin and actin in the mouse kidney brush-border membrane bind to and are degraded by meprins, an interaction that contributes to injury in ischemia-reperfusion.在小鼠肾脏刷状缘膜中，微绒毛蛋白与肌动蛋白结合，并被微绒毛蛋白降解，这种相互作用有助于缺血再灌注损伤。
Am J Physiol Renal Physiol. 2011 Oct;301(4):F871-82. doi: 10.1152/ajprenal.00703.2010. Epub 2011 Jul 27.
6
Analyzing the protease web in skin: meprin metalloproteases are activated specifically by KLK4, 5 and 8 vice versa leading to processing of proKLK7 thereby triggering its activation.分析皮肤中的蛋白酶网络：Meprin 金属蛋白酶特异性地被 KLK4、5 和 8 激活，反过来又导致 proKLK7 的加工，从而触发其激活。
Biol Chem. 2010 Apr;391(4):455-60. doi: 10.1515/BC.2010.023.
7
Meprin A and meprin alpha generate biologically functional IL-1beta from pro-IL-1beta.膜金属蛋白酶A和膜金属蛋白酶α可从白细胞介素-1前体生成具有生物学功能的白细胞介素-1β。
Biochem Biophys Res Commun. 2009 Feb 20;379(4):904-8. doi: 10.1016/j.bbrc.2008.12.161. Epub 2009 Jan 7.
8
Meprin metalloproteases inactivate interleukin 6.金属蛋白酶 Meprin 使白细胞介素 6 失活。
J Biol Chem. 2014 Mar 14;289(11):7580-8. doi: 10.1074/jbc.M113.546309. Epub 2014 Jan 28.
9
Basement membrane protein nidogen-1 is a target of meprin β in cisplatin nephrotoxicity.基底膜蛋白巢蛋白-1是meprin β在顺铂肾毒性中的作用靶点。
Toxicol Lett. 2015 Jul 16;236(2):110-6. doi: 10.1016/j.toxlet.2015.05.005. Epub 2015 May 6.
10
Cysteine mutations in the MAM domain result in monomeric meprin and alter stability and activity of the proteinase.MAM结构域中的半胱氨酸突变导致单体膜金属蛋白酶，并改变蛋白酶的稳定性和活性。
J Biol Chem. 1996 Sep 27;271(39):24236-41. doi: 10.1074/jbc.271.39.24236.

引用本文的文献

1
CCL2 promotes proliferation, migration and angiogenesis through the MAPK/ERK1/2/MMP9, PI3K/AKT, Wnt/β‑catenin signaling pathways in HUVECs.CCL2通过MAPK/ERK1/2/MMP9、PI3K/AKT、Wnt/β-连环蛋白信号通路促进人脐静脉内皮细胞（HUVECs）的增殖、迁移和血管生成。
Exp Ther Med. 2022 Dec 27;25(2):77. doi: 10.3892/etm.2022.11776. eCollection 2023 Feb.
2
Helical ultrastructure of the metalloprotease meprin α in complex with a small molecule inhibitor.金属蛋白酶 meprin α 与小分子抑制剂复合物的螺旋超微结构。
Nat Commun. 2022 Oct 19;13(1):6178. doi: 10.1038/s41467-022-33893-7.
3
Meprin-β activity modulates the β-catalytic subunit of protein kinase A in ischemia-reperfusion-induced acute kidney injury.

本文引用的文献

1
Monocyte chemoattractant protein-1 and the kidney.单核细胞趋化蛋白-1与肾脏
Curr Opin Nephrol Hypertens. 2016 Jan;25(1):42-9. doi: 10.1097/MNH.0000000000000186.
2
Isoform-specific interactions between meprin metalloproteases and the catalytic subunit of protein kinase A: significance in acute and chronic kidney injury.金属蛋白酶 meprin 同工型与蛋白激酶 A 催化亚基的同工型特异性相互作用：在急性和慢性肾损伤中的意义。
Am J Physiol Renal Physiol. 2015 Jan 1;308(1):F56-68. doi: 10.1152/ajprenal.00167.2014. Epub 2014 Oct 29.
3
The chemokine (C-C motif) ligand 2 in neuroinflammation and neurodegeneration.
Meprin-β 活性调节缺血再灌注诱导的急性肾损伤中的蛋白激酶 A 的β-催化亚基。
Am J Physiol Renal Physiol. 2020 May 1;318(5):F1147-F1159. doi: 10.1152/ajprenal.00571.2019. Epub 2020 Mar 16.
4
Inhibition of miR-155-5p Exerts Anti-Fibrotic Effects in Silicotic Mice by Regulating Meprin α.抑制miR-155-5p通过调控金属蛋白酶解整合素因子α对矽肺小鼠发挥抗纤维化作用。
Mol Ther Nucleic Acids. 2020 Mar 6;19:350-360. doi: 10.1016/j.omtn.2019.11.018. Epub 2019 Nov 26.
5
LC-MS-based metabolomics analysis to identify meprin-β-associated changes in kidney tissue from mice with STZ-induced type 1 diabetes and diabetic kidney injury.基于 LC-MS 的代谢组学分析鉴定 STZ 诱导的 1 型糖尿病和糖尿病肾病损伤小鼠肾脏组织中 meprin-β 相关变化。
Am J Physiol Renal Physiol. 2019 Oct 1;317(4):F1034-F1046. doi: 10.1152/ajprenal.00166.2019. Epub 2019 Aug 14.
6
Meprin β metalloproteases associated with differential metabolite profiles in the plasma and urine of mice with type 1 diabetes and diabetic nephropathy.与1型糖尿病和糖尿病肾病小鼠血浆及尿液中差异代谢物谱相关的Meprin β金属蛋白酶
BMC Nephrol. 2019 Apr 25;20(1):141. doi: 10.1186/s12882-019-1313-2.
7
Role of meprin metalloproteinases in cytokine processing and inflammation.金属蛋白酶 meprin 在细胞因子加工和炎症中的作用。
Cytokine. 2019 Feb;114:18-25. doi: 10.1016/j.cyto.2018.11.032. Epub 2018 Dec 20.
8
Undiagnosed Kidney Injury in Uninsured and Underinsured Diabetic African American Men and Putative Role of Meprin Metalloproteases in Diabetic Nephropathy.未参保及参保不足的非裔美国糖尿病男性的未诊断肾损伤以及金属蛋白酶在糖尿病肾病中的假定作用
Int J Nephrol. 2018 Apr 29;2018:6753489. doi: 10.1155/2018/6753489. eCollection 2018.
神经炎症和神经退行性变中的趋化因子（C-C基序）配体2
Adv Exp Med Biol. 2014;824:209-19. doi: 10.1007/978-3-319-07320-0_15.
4
Cytokines and chemokines: At the crossroads of cell signalling and inflammatory disease.细胞因子与趋化因子：处于细胞信号传导和炎症性疾病的交叉点
Biochim Biophys Acta. 2014 Nov;1843(11):2563-2582. doi: 10.1016/j.bbamcr.2014.05.014. Epub 2014 Jun 2.
5
Impact of MCP-1 in atherosclerosis.单核细胞趋化蛋白-1在动脉粥样硬化中的作用
Curr Pharm Des. 2014;20(28):4580-8. doi: 10.2174/1381612820666140522115801.
6
Meprin metalloproteases inactivate interleukin 6.金属蛋白酶 Meprin 使白细胞介素 6 失活。
J Biol Chem. 2014 Mar 14;289(11):7580-8. doi: 10.1074/jbc.M113.546309. Epub 2014 Jan 28.
7
Amniotic fluid stem cells inhibit the progression of bleomycin-induced pulmonary fibrosis via CCL2 modulation in bronchoalveolar lavage.羊膜干细胞通过支气管肺泡灌洗液中 CCL2 的调节抑制博来霉素诱导的肺纤维化的进展。
PLoS One. 2013 Aug 13;8(8):e71679. doi: 10.1371/journal.pone.0071679. eCollection 2013.
8
Meprin A impairs epithelial barrier function, enhances monocyte migration, and cleaves the tight junction protein occludin.Meprin A 损害上皮屏障功能，增强单核细胞迁移，并裂解紧密连接蛋白 occludin。
Am J Physiol Renal Physiol. 2013 Sep 1;305(5):F714-26. doi: 10.1152/ajprenal.00179.2012. Epub 2013 Jun 26.
9
Meprin A metalloproteinase and its role in acute kidney injury.金属蛋白酶 Meprin A 及其在急性肾损伤中的作用。
Am J Physiol Renal Physiol. 2013 May 1;304(9):F1150-8. doi: 10.1152/ajprenal.00014.2013. Epub 2013 Feb 20.
10
The metalloproteases meprin α and meprin β: unique enzymes in inflammation, neurodegeneration, cancer and fibrosis.金属蛋白酶 meprin α 和 meprin β：炎症、神经退行性变、癌症和纤维化中的独特酶。
Biochem J. 2013 Mar 1;450(2):253-64. doi: 10.1042/BJ20121751.