• 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

3,5,3'-三碘-L-甲状腺原氨酸通过αvβ3整合素调节缺氧条件下分化型PC-12细胞中肌动蛋白细胞骨架的动态变化。

3,5,3'-Triiodo-L-Thyronine Regulates Actin Cytoskeleton Dynamic in The Differentiated PC-12 Cells during Hypoxia through An αvβ3 Integrin.

作者信息

Barbakadze Tamar, Kvergelidze Elisabed, Bátor Judit, Szeberényi József, Mikeladze David

机构信息

Faculty of Natural Sciences and Medicine, Ilia State University, Tbilisi, Georgia.

Laboratory of Biochemistry, Ivane Beritashvili Center of Experimental Biomedicine, Tbilisi, Georgia.

出版信息

Cell J. 2023 Apr 1;25(4):247-254. doi: 10.22074/cellj.2022.557501.1059.

DOI:10.22074/cellj.2022.557501.1059
PMID:37210645
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10201356/
Abstract

OBJECTIVE

Thyroid hormones are involved in the pathogenesis of various neurological disorders. Ischemia/hypoxia that induces rigidity of the actin filaments, which initiates neurodegeneration and reduces synaptic plasticity. We hypothesized that thyroid hormones via alpha-v-beta-3 (αvβ3) integrin could regulate the actin filament rearrangement during hypoxia and increase neuronal cell viability.

MATERIALS AND METHODS

In this experimental study, we analysed the dynamics of actin cytoskeleton according to the G/F actin ratio, cofilin-1/p-cofilin-1 ratio, and p-Fyn/Fyn ratio in differentiated PC-12 cells with/without T3 hormone (3,5,3'-triiodo-L-thyronine) treatment and blocking αvβ3-integrin-antibody under hypoxic conditions using electrophoresis and western blotting methods. We assessed NADPH oxidase activity under the hypoxic condition by the luminometric method and Rac1 activity using the ELISA-based (G-LISA) activation assay kit.

RESULTS

The T3 hormone induces the αvβ3 integrin-dependent dephosphorylation of the Fyn kinase (P=0.0010), modulates the G/F actin ratio (P=0.0010) and activates the Rac1/NADPH oxidase/cofilin-1 (P=0.0069, P=0.0010, P=0.0045) pathway. T3 increases PC-12 cell viability (P=0.0050) during hypoxia via αvβ3 integrin-dependent downstream regulation systems.

CONCLUSION

The T3 thyroid hormone may modulate the G/F actin ratio via the Rac1 GTPase/NADPH oxidase/ cofilin1signaling pathway and αvβ3-integrin-dependent suppression of Fyn kinase phosphorylation.

摘要

目的

甲状腺激素参与多种神经疾病的发病机制。缺血/缺氧会导致肌动蛋白丝僵硬，引发神经退行性变并降低突触可塑性。我们推测甲状腺激素通过α - v - β - 3（αvβ3）整合素可在缺氧时调节肌动蛋白丝重排并提高神经元细胞活力。

材料与方法

在本实验研究中，我们使用电泳和蛋白质印迹法，分析了在缺氧条件下，经/未经T3激素（3,5,3'-三碘 - L - 甲状腺原氨酸）处理以及用αvβ3整合素抗体阻断的分化PC - 12细胞中，根据G/F肌动蛋白比率、丝切蛋白 - 1/p - 丝切蛋白 - 1比率和p - Fyn/Fyn比率所反映的肌动蛋白细胞骨架动力学。我们通过发光法评估缺氧条件下的NADPH氧化酶活性，并使用基于酶联免疫吸附测定（G - LISA）的激活检测试剂盒评估Rac1活性。

结果

T3激素诱导Fyn激酶的αvβ3整合素依赖性去磷酸化（P = 0.0010），调节G/F肌动蛋白比率（P = 0.0010）并激活Rac1/NADPH氧化酶/丝切蛋白 - 1（P = 0.0069，P = 0.0010，P = 0.0045）信号通路。T3通过αvβ3整合素依赖性下游调节系统在缺氧期间提高PC - 12细胞活力（P = 0.0050）。

结论

T3甲状腺激素可能通过Rac1 GTP酶/NADPH氧化酶/丝切蛋白1信号通路以及αvβ3整合素依赖性抑制Fyn激酶磷酸化来调节G/F肌动蛋白比率。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f5/10201356/217662a9968f/Cell-J-25-247-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f5/10201356/00a2da5d8664/Cell-J-25-247-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f5/10201356/bf01d72f99c7/Cell-J-25-247-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f5/10201356/3ab2b02e7f26/Cell-J-25-247-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f5/10201356/b9394d705a9f/Cell-J-25-247-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f5/10201356/465bf481b3b1/Cell-J-25-247-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f5/10201356/217662a9968f/Cell-J-25-247-g06.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f5/10201356/00a2da5d8664/Cell-J-25-247-g01.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f5/10201356/bf01d72f99c7/Cell-J-25-247-g02.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f5/10201356/3ab2b02e7f26/Cell-J-25-247-g03.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f5/10201356/b9394d705a9f/Cell-J-25-247-g04.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f5/10201356/465bf481b3b1/Cell-J-25-247-g05.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/92f5/10201356/217662a9968f/Cell-J-25-247-g06.jpg

相似文献

1
3,5,3'-Triiodo-L-Thyronine Regulates Actin Cytoskeleton Dynamic in The Differentiated PC-12 Cells during Hypoxia through An αvβ3 Integrin.3,5,3'-三碘-L-甲状腺原氨酸通过αvβ3整合素调节缺氧条件下分化型PC-12细胞中肌动蛋白细胞骨架的动态变化。
Cell J. 2023 Apr 1;25(4):247-254. doi: 10.22074/cellj.2022.557501.1059.
2
Thyroid hormone T3 induces Fyn modification and modulates palmitoyltransferase gene expression through αvβ3 integrin receptor in PC12 cells during hypoxia.甲状腺激素T3在缺氧条件下通过αvβ3整合素受体诱导PC12细胞中Fyn修饰并调节棕榈酰转移酶基因表达。
Transl Neurosci. 2024 Aug 7;15(1):20220347. doi: 10.1515/tnsci-2022-0347. eCollection 2024 Jan 1.
3
Thyroid hormones differentially regulate phosphorylation of ERK and Akt via integrin αvβ3 receptor in undifferentiated and differentiated PC-12 cells.甲状腺激素通过未分化和分化的 PC-12 细胞中的整合素 αvβ3 受体差异调节 ERK 和 Akt 的磷酸化。
Cell Biochem Funct. 2014 Apr;32(3):282-6. doi: 10.1002/cbf.3013. Epub 2013 Nov 11.
4
The thyroid hormone-αvβ3 integrin axis in ovarian cancer: regulation of gene transcription and MAPK-dependent proliferation.甲状腺激素-αvβ3 整联蛋白轴在卵巢癌中的作用：基因转录调控和 MAPK 依赖性增殖。
Oncogene. 2016 Apr 14;35(15):1977-87. doi: 10.1038/onc.2015.262. Epub 2015 Jul 13.
5
Porcine Hemagglutinating Encephalomyelitis Virus Activation of the Integrin α5β1-FAK-Cofilin Pathway Causes Cytoskeletal Rearrangement To Promote Its Invasion of N2a Cells.猪传染性脑脊髓炎病毒激活整合素 α5β1-FAK-丝切蛋白通路导致细胞骨架重排促进其对 N2a 细胞的侵袭。
J Virol. 2019 Feb 19;93(5). doi: 10.1128/JVI.01736-18. Print 2019 Mar 1.
6
Angiopoietin-like 3 induces podocyte F-actin rearrangement through integrin α(V)β₃/FAK/PI3K pathway-mediated Rac1 activation.血管生成素样蛋白 3 通过整合素 α(V)β₃/FAK/PI3K 通路介导线粒体 Rac1 的激活诱导足细胞 F-肌动蛋白重排。
Biomed Res Int. 2013;2013:135608. doi: 10.1155/2013/135608. Epub 2013 Nov 5.
7
Molecular Basis of Nongenomic Actions of Thyroid Hormone.甲状腺激素非基因组作用的分子基础
Vitam Horm. 2018;106:67-96. doi: 10.1016/bs.vh.2017.06.001. Epub 2017 Jul 8.
8
Crosstalk between integrin αvβ3 and ERα contributes to thyroid hormone-induced proliferation of ovarian cancer cells.整合素αvβ3与雌激素受体α之间的相互作用促进甲状腺激素诱导的卵巢癌细胞增殖。
Oncotarget. 2017 Apr 11;8(15):24237-24249. doi: 10.18632/oncotarget.10757.
9
Coronaviruses and Integrin αvβ3: Does Thyroid Hormone Modify the Relationship?冠状病毒和整合素 αvβ3：甲状腺激素是否改变了这种关系？
Endocr Res. 2020 Aug;45(3):210-215. doi: 10.1080/07435800.2020.1767127.
10
Cancer Cell Gene Expression Modulated from Plasma Membrane Integrin αvβ3 by Thyroid Hormone and Nanoparticulate Tetrac.甲状腺激素和纳米颗粒四碘甲状腺原氨酸通过质膜整合素αvβ3调节癌细胞基因表达
Front Endocrinol (Lausanne). 2015 Jan 12;5:240. doi: 10.3389/fendo.2014.00240. eCollection 2014.

引用本文的文献

1
Thyroid hormone T3 induces Fyn modification and modulates palmitoyltransferase gene expression through αvβ3 integrin receptor in PC12 cells during hypoxia.甲状腺激素T3在缺氧条件下通过αvβ3整合素受体诱导PC12细胞中Fyn修饰并调节棕榈酰转移酶基因表达。
Transl Neurosci. 2024 Aug 7;15(1):20220347. doi: 10.1515/tnsci-2022-0347. eCollection 2024 Jan 1.

本文引用的文献

1
Fyn Kinase-Mediated PKCδ Y311 Phosphorylation Induces Dopaminergic Degeneration in Cell Culture and Animal Models: Implications for the Identification of a New Pharmacological Target for Parkinson's Disease.Fyn激酶介导的PKCδ Y311磷酸化在细胞培养和动物模型中诱导多巴胺能神经元变性：对帕金森病新药理学靶点鉴定的启示
Front Pharmacol. 2021 Apr 28;12:631375. doi: 10.3389/fphar.2021.631375. eCollection 2021.
2
Fyn Tyrosine Kinase as Harmonizing Factor in Neuronal Functions and Dysfunctions.Fyn 酪氨酸激酶作为神经元功能和失调的协调因子。
Int J Mol Sci. 2020 Jun 22;21(12):4444. doi: 10.3390/ijms21124444.
3
Thyroid Hormones in the Brain and Their Impact in Recovery Mechanisms After Stroke.
甲状腺激素在大脑中的作用及其对中风后恢复机制的影响。
Front Neurol. 2019 Oct 18;10:1103. doi: 10.3389/fneur.2019.01103. eCollection 2019.
4
Sodium nitroprusside induces H-Ras depalmitoylation and alters the cellular response to hypoxia in differentiated and undifferentiated PC12 cells.硝普钠诱导 H-Ras 去棕榈酰化，并改变分化和未分化 PC12 细胞对缺氧的细胞反应。
Cell Biochem Funct. 2019 Oct;37(7):545-552. doi: 10.1002/cbf.3431. Epub 2019 Aug 19.
5
Actin(g) on mitochondria - a role for cofilin1 in neuronal cell death pathways.肌动蛋白（g）作用于线粒体-胞磷胆碱 1 在神经元细胞死亡途径中的作用。
Biol Chem. 2019 Aug 27;400(9):1089-1097. doi: 10.1515/hsz-2019-0120.
6
Molecular Basis of Nongenomic Actions of Thyroid Hormone.甲状腺激素非基因组作用的分子基础
Vitam Horm. 2018;106:67-96. doi: 10.1016/bs.vh.2017.06.001. Epub 2017 Jul 8.
7
Thyroid hormone and the brain: Mechanisms of action in development and role in protection and promotion of recovery after brain injury.甲状腺激素与大脑：在发育过程中的作用机制及其在脑损伤保护和促进恢复中的作用。
Pharmacol Ther. 2018 Jun;186:176-185. doi: 10.1016/j.pharmthera.2018.01.007. Epub 2018 Feb 9.
8
Actin polymerization is reduced in the anterior cingulate cortex of elderly patients with schizophrenia.老年精神分裂症患者扣带回前部皮质的肌动蛋白聚合减少。
Transl Psychiatry. 2017 Dec 11;7(12):1278. doi: 10.1038/s41398-017-0045-y.
9
Thyroid dysfunction in children with autism spectrum disorder is associated with folate receptor α autoimmune disorder.自闭症谱系障碍儿童的甲状腺功能障碍与α-叶酸受体自身免疫性疾病有关。
J Neuroendocrinol. 2017 Mar;29(3). doi: 10.1111/jne.12461.
10
Hypoxia and the modulation of the actin cytoskeleton - emerging interrelations.缺氧与肌动蛋白细胞骨架的调节——新出现的相互关系
Hypoxia (Auckl). 2014 Mar 25;2:11-21. doi: 10.2147/HP.S53575. eCollection 2014.