• 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

组织蛋白酶B基因敲除小鼠肾皮质膜组分中MARCKS蛋白表达降低与溶血磷脂酰胆碱及蛋白激酶C活性降低有关。

Decreased MARCKS Protein Expression in Kidney Cortex Membrane Fractions of Cathepsin B Knockout Mice Is Associated with Reduced Lysophosphatidylcholine and Protein Kinase C Activity.

作者信息

Kawakibi Tamim, Bala Niharika, Liu Lauren P, Searcy Louis A, Denslow Nancy D, Alli Abdel A

机构信息

Department of Physiology and Aging, University of Florida College of Medicine, Gainesville, FL 32610, USA.

Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida College of Veterinary Medicine, Gainesville, FL 32610, USA.

出版信息

Biomedicines. 2023 May 20;11(5):1489. doi: 10.3390/biomedicines11051489.

DOI:10.3390/biomedicines11051489
PMID:37239160
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10216610/
Abstract

Cathpesin B is a multi-functional protease that plays numerous roles in physiology and pathophysiology. We hypothesized that actin cytoskeleton proteins that are substrates of cathepsin B, various lipids, and kinases that are regulated by lipids would be down-regulated in the kidney of cathepsin B knockout mice. Here, we show by Western blot and densitometric analysis that the expression and proteolysis of the actin cytoskeleton proteins myristoylated alanine-rich C-kinase substrate (MARCKS) and spectrin are significantly reduced in kidney cortex membrane fractions of cathepsin B knockout mice compared to C57B6 wild-type control mice. Lipidomic results show that specific lipids are increased while other lipids, including lysophosphatidylcholine (LPC) species LPC (16:0), LPC (18:0), LPC (18:1), and LPC (18:2), are significantly decreased in membrane fractions of the kidney cortex from Cathepsin B null mice. Protein Kinase C (PKC) activity is significantly lower in the kidney cortex of cathepsin B knockout mice compared to wild-type mice, while calcium/calmodulin-dependent protein kinase II (CaMKII) activity and phospholipase D (PLD) activity are comparable between the two groups. Together, these results provide the first evidence of altered actin cytoskeleton organization, membrane lipid composition, and PKC activity in the kidneys of mice lacking cathepsin B.

摘要

组织蛋白酶B是一种多功能蛋白酶，在生理和病理生理过程中发挥着多种作用。我们推测，作为组织蛋白酶B底物的肌动蛋白细胞骨架蛋白、各种脂质以及受脂质调节的激酶，在组织蛋白酶B基因敲除小鼠的肾脏中会下调。在此，我们通过蛋白质印迹法和光密度分析表明，与C57B6野生型对照小鼠相比，组织蛋白酶B基因敲除小鼠肾皮质膜组分中富含肉豆蔻酰化丙氨酸的蛋白激酶C底物（MARCKS）和血影蛋白等肌动蛋白细胞骨架蛋白的表达和蛋白水解显著降低。脂质组学结果显示，组织蛋白酶B基因敲除小鼠肾皮质膜组分中特定脂质增加，而其他脂质，包括溶血磷脂酰胆碱（LPC）种类LPC（16:0）、LPC（18:0）、LPC（18:1）和LPC（18:2）显著减少。与野生型小鼠相比，组织蛋白酶B基因敲除小鼠肾皮质中的蛋白激酶C（PKC）活性显著降低，而两组之间钙/钙调蛋白依赖性蛋白激酶II（CaMKII）活性和磷脂酶D（PLD）活性相当。总之，这些结果首次证明了在缺乏组织蛋白酶B的小鼠肾脏中，肌动蛋白细胞骨架组织、膜脂质组成和PKC活性发生了改变。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378d/10216610/3828fccc1742/biomedicines-11-01489-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378d/10216610/8523de033d03/biomedicines-11-01489-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378d/10216610/e1fb55f30649/biomedicines-11-01489-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378d/10216610/205247057a85/biomedicines-11-01489-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378d/10216610/969c0367446c/biomedicines-11-01489-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378d/10216610/5e70e38ecad2/biomedicines-11-01489-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378d/10216610/3828fccc1742/biomedicines-11-01489-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378d/10216610/8523de033d03/biomedicines-11-01489-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378d/10216610/e1fb55f30649/biomedicines-11-01489-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378d/10216610/205247057a85/biomedicines-11-01489-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378d/10216610/969c0367446c/biomedicines-11-01489-g004a.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378d/10216610/5e70e38ecad2/biomedicines-11-01489-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/378d/10216610/3828fccc1742/biomedicines-11-01489-g006.jpg

相似文献

1
Decreased MARCKS Protein Expression in Kidney Cortex Membrane Fractions of Cathepsin B Knockout Mice Is Associated with Reduced Lysophosphatidylcholine and Protein Kinase C Activity.组织蛋白酶B基因敲除小鼠肾皮质膜组分中MARCKS蛋白表达降低与溶血磷脂酰胆碱及蛋白激酶C活性降低有关。
Biomedicines. 2023 May 20;11(5):1489. doi: 10.3390/biomedicines11051489.
2
Augmentation of Cathepsin Isoforms in Diabetic db/db Mouse Kidneys Is Associated with an Increase in Renal MARCKS Expression and Proteolysis.糖尿病 db/db 小鼠肾脏中组织蛋白酶同工酶的增加与 MARCKS 表达和蛋白水解的增加有关。
Int J Mol Sci. 2023 Aug 5;24(15):12484. doi: 10.3390/ijms241512484.
3
Adducin is an in vivo substrate for protein kinase C: phosphorylation in the MARCKS-related domain inhibits activity in promoting spectrin-actin complexes and occurs in many cells, including dendritic spines of neurons.内收蛋白是蛋白激酶C的一种体内底物：在与富含丙氨酸的豆蔻酰化蛋白激酶C底物（MARCKS）相关的结构域中的磷酸化会抑制其促进血影蛋白-肌动蛋白复合物形成的活性，且这种磷酸化发生在包括神经元树突棘在内的许多细胞中。
J Cell Biol. 1998 Jul 27;142(2):485-97. doi: 10.1083/jcb.142.2.485.
4
Calmodulin and CaMKII modulate ENaC activity by regulating the association of MARCKS and the cytoskeleton with the apical membrane.钙调蛋白和钙/钙调蛋白依赖性蛋白激酶II通过调节富含丙氨酸的蛋白激酶C底物（MARCKS）和细胞骨架与顶端膜的结合来调节上皮钠通道（ENaC）的活性。
Am J Physiol Renal Physiol. 2015 Sep 1;309(5):F456-63. doi: 10.1152/ajprenal.00631.2014. Epub 2015 Jul 1.
5
Overexpression of myristoylated alanine-rich C-kinase substrate enhances activation of phospholipase D by protein kinase C in SK-N-MC human neuroblastoma cells.肉豆蔻酰化富含丙氨酸的蛋白激酶C底物的过表达增强了蛋白激酶C在人神经母细胞瘤SK-N-MC细胞中对磷脂酶D的激活作用。
Biochem J. 1998 Jun 1;332 ( Pt 2)(Pt 2):321-7. doi: 10.1042/bj3320321.
6
Identification and characterization of cathepsin B as the cellular MARCKS cleaving enzyme.组织蛋白酶B作为细胞MARCKS切割酶的鉴定与表征
J Biol Chem. 1997 Sep 19;272(38):23833-42. doi: 10.1074/jbc.272.38.23833.
7
Activation of phospholipase D by PKC and GTPgammaS in human neuroblastoma cells overexpressing MARCKS.在过表达MARCKS的人神经母细胞瘤细胞中，蛋白激酶C和GTPγS对磷脂酶D的激活作用。
Biochim Biophys Acta. 2000 Sep 27;1487(2-3):177-89. doi: 10.1016/s1388-1981(00)00094-9.
8
Calmodulin and protein kinase C cross-talk: the MARCKS protein is an actin filament and plasma membrane cross-linking protein regulated by protein kinase C phosphorylation and by calmodulin.钙调蛋白与蛋白激酶C的相互作用：MARCKS蛋白是一种肌动蛋白丝和质膜交联蛋白，受蛋白激酶C磷酸化和钙调蛋白调控。
Ciba Found Symp. 1992;164:145-54; discussion 154-61. doi: 10.1002/9780470514207.ch10.
9
Functional involvement of protein kinase C-betaII and its substrate, myristoylated alanine-rich C-kinase substrate (MARCKS), in insulin-stimulated glucose transport in L6 rat skeletal muscle cells.蛋白激酶C-βII及其底物富含肉豆蔻酰化丙氨酸的C激酶底物（MARCKS）在L6大鼠骨骼肌细胞胰岛素刺激的葡萄糖转运中的功能参与
Diabetologia. 2009 May;52(5):901-11. doi: 10.1007/s00125-009-1298-7. Epub 2009 Feb 28.
10
Differential expression and regulation of myristoylated alanine-rich C kinase substrate (MARCKS) in the hippocampus of C57/BL6J and DBA/2J mice.C57/BL6J和DBA/2J小鼠海马中肉豆蔻酰化富含丙氨酸的C激酶底物（MARCKS）的差异表达与调控
J Neurochem. 2003 Apr;85(2):462-8. doi: 10.1046/j.1471-4159.2003.01700.x.

引用本文的文献

1
Cathepsin B Levels Correlate with the Severity of Canine Myositis.组织蛋白酶B水平与犬类肌炎的严重程度相关。
Biomolecules. 2025 May 21;15(5):743. doi: 10.3390/biom15050743.
2
Cathepsin B induces kidney diseases through different types of programmed cell death.组织蛋白酶B通过不同类型的程序性细胞死亡诱导肾脏疾病。
Front Immunol. 2025 Mar 10;16:1535313. doi: 10.3389/fimmu.2025.1535313. eCollection 2025.
3
Mycobacterium avium inhibits protein kinase C and MARCKS phosphorylation in human cystic fibrosis and non-cystic fibrosis cells.

本文引用的文献

1
A Theranostic Small-Molecule Prodrug Conjugate for Neuroendocrine Prostate Cancer.一种用于神经内分泌前列腺癌的诊疗小分子前药缀合物。
Pharmaceutics. 2023 Feb 1;15(2):481. doi: 10.3390/pharmaceutics15020481.
2
Dapagliflozin Treatment Augments Bioactive Phosphatidylethanolamine Concentrations in Kidney Cortex Membrane Fractions of Hypertensive Diabetic db/db Mice and Alters the Density of Lipid Rafts in Mouse Proximal Tubule Cells.达格列净治疗可增加高血压糖尿病 db/db 小鼠肾脏皮质膜部分的生物活性磷脂酰乙醇胺浓度，并改变小鼠近端肾小管细胞中脂筏的密度。
Int J Mol Sci. 2023 Jan 11;24(2):1408. doi: 10.3390/ijms24021408.
3
Human Alpha-1 Antitrypsin Attenuates ENaC and MARCKS and Lowers Blood Pressure in Hypertensive Diabetic db/db Mice.
鸟分枝杆菌抑制人囊性纤维化和非囊性纤维化细胞中的蛋白激酶 C 和 MARCKS 磷酸化。
PLoS One. 2024 Oct 16;19(10):e0308299. doi: 10.1371/journal.pone.0308299. eCollection 2024.
人α-1 抗胰蛋白酶可减弱 ENaC 和 MARCKS，降低糖尿病 db/db 高血压小鼠的血压。
Biomolecules. 2022 Dec 29;13(1):66. doi: 10.3390/biom13010066.
4
Kidney tubular epithelial cell ferroptosis links glomerular injury to tubulointerstitial pathology in lupus nephritis.狼疮性肾炎中肾脏管状上皮细胞铁死亡将肾小球损伤与肾小管间质病变联系起来。
Clin Immunol. 2023 Mar;248:109213. doi: 10.1016/j.clim.2022.109213. Epub 2022 Dec 22.
5
Theranostic Small-Molecule Prodrug Conjugates for Targeted Delivery and Controlled Release of Toll-like Receptor 7 Agonists.用于靶向递呈和 Toll 样受体 7 激动剂控释的治疗诊断小分子前药偶联物。
Int J Mol Sci. 2022 Jun 28;23(13):7160. doi: 10.3390/ijms23137160.
6
Tempol Alters Urinary Extracellular Vesicle Lipid Content and Release While Reducing Blood Pressure during the Development of Salt-Sensitive Hypertension.替普瑞醇通过降低血压改变盐敏感性高血压发展过程中的尿细胞外囊泡脂质含量和释放。
Biomolecules. 2021 Dec 1;11(12):1804. doi: 10.3390/biom11121804.
7
Lysophosphatidylcholine mediates fast decline in kidney function in diabetic kidney disease.溶血磷脂酰胆碱介导糖尿病肾病肾功能的快速下降。
Kidney Int. 2022 Mar;101(3):510-526. doi: 10.1016/j.kint.2021.10.039. Epub 2021 Nov 29.
8
Membrane to cytosol redistribution of αII-spectrin drives extracellular vesicle biogenesis in malignant breast cells.αII- spectrin 从膜到细胞质的重新分布驱动恶性乳腺细胞外囊泡的生物发生。
Proteomics. 2021 Jul;21(13-14):e2000091. doi: 10.1002/pmic.202000091. Epub 2021 May 19.
9
Cathepsin B is an executioner of ferroptosis.组织蛋白酶 B 是铁死亡的执行者。
Biochim Biophys Acta Mol Cell Res. 2021 Mar;1868(3):118928. doi: 10.1016/j.bbamcr.2020.118928. Epub 2020 Dec 17.
10
Cathepsin B is a mediator of organelle-specific initiation of ferroptosis.组织蛋白酶 B 是细胞器特异性铁死亡起始的介质。
Biochem Biophys Res Commun. 2020 Dec 17;533(4):1464-1469. doi: 10.1016/j.bbrc.2020.10.035. Epub 2020 Oct 22.