• 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

D-半胱氨酸通过生成硫化氢和激活 Nrf2 激活小脑浦肯野细胞中的伴侣介导的自噬。

D-Cysteine Activates Chaperone-Mediated Autophagy in Cerebellar Purkinje Cells via the Generation of Hydrogen Sulfide and Nrf2 Activation.

机构信息

Department of Chemico-Pharmacological Sciences, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.

Department of Neurophysiology & Neural Repair, Graduate School of Medicine, Gunma University, Maebashi 371-8511, Japan.

出版信息

Cells. 2022 Apr 5;11(7):1230. doi: 10.3390/cells11071230.

DOI:10.3390/cells11071230
PMID:35406792
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8997644/
Abstract

Chaperone-mediated autophagy (CMA) is a pathway in the autophagy-lysosome protein degradation system. CMA impairment has been implicated to play a role in spinocerebellar ataxia (SCA) pathogenesis. D-cysteine is metabolized by D-amino acid oxidase (DAO), leading to hydrogen sulfide generation in the cerebellum. Although D-cysteine alleviates the disease phenotypes in SCA-model mice, it remains unknown how hydrogen sulfide derived from D-cysteine exerts this effect. In the present study, we investigated the effects of D-cysteine and hydrogen sulfide on CMA activity using a CMA activity marker that we have established. D-cysteine activated CMA in Purkinje cells (PCs) of primary cerebellar cultures where DAO was expressed, while it failed to activate CMA in DAO-deficient AD293 cells. In contrast, NaS, a hydrogen sulfide donor, activated CMA in both PCs and AD293 cells. Nuclear factor erythroid 2-related factor 2 (Nrf2) is known to be activated by hydrogen sulfide and regulate CMA activity. An Nrf2 inhibitor, ML385, prevented CMA activation triggered by D-cysteine and NaS. Additionally, long-term treatment with D-cysteine increased the amounts of Nrf2 and LAMP2A, a CMA-related protein, in the mouse cerebellum. These findings suggest that hydrogen sulfide derived from D-cysteine enhances CMA activity via Nrf2 activation.

摘要

伴侣蛋白介导的自噬（CMA）是自噬溶酶体蛋白降解系统中的一种途径。CMA 功能障碍被认为在脊髓小脑共济失调（SCA）发病机制中起作用。D-半胱氨酸被 D-氨基酸氧化酶（DAO）代谢，导致小脑中硫化氢的生成。尽管 D-半胱氨酸减轻了 SCA 模型小鼠的疾病表型，但尚不清楚 D-半胱氨酸衍生的硫化氢如何发挥这种作用。在本研究中，我们使用我们建立的 CMA 活性标记物研究了 D-半胱氨酸和硫化氢对 CMA 活性的影响。D-半胱氨酸在表达 DAO 的原代小脑培养物中的浦肯野细胞（PC）中激活 CMA，但在缺乏 DAO 的 AD293 细胞中无法激活 CMA。相比之下，硫化氢供体 NaS 激活了 PC 和 AD293 细胞中的 CMA。核因子红细胞 2 相关因子 2（Nrf2）已知被硫化氢激活并调节 CMA 活性。Nrf2 抑制剂 ML385 可阻止 D-半胱氨酸和 NaS 触发的 CMA 激活。此外，长期用 D-半胱氨酸处理可增加小鼠小脑 Nrf2 和 LAMP2A（一种与 CMA 相关的蛋白）的含量。这些发现表明，D-半胱氨酸衍生的硫化氢通过 Nrf2 激活增强 CMA 活性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/a10b78d8c759/cells-11-01230-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/70b05c4552aa/cells-11-01230-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/75fc7ed035b4/cells-11-01230-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/650e0e2c00ca/cells-11-01230-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/45d081a87163/cells-11-01230-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/f11f5fe3c394/cells-11-01230-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/4f0ec774be31/cells-11-01230-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/5875048aaf37/cells-11-01230-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/a10b78d8c759/cells-11-01230-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/70b05c4552aa/cells-11-01230-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/75fc7ed035b4/cells-11-01230-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/650e0e2c00ca/cells-11-01230-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/45d081a87163/cells-11-01230-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/f11f5fe3c394/cells-11-01230-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/4f0ec774be31/cells-11-01230-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/5875048aaf37/cells-11-01230-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7456/8997644/a10b78d8c759/cells-11-01230-g008.jpg

相似文献

1
D-Cysteine Activates Chaperone-Mediated Autophagy in Cerebellar Purkinje Cells via the Generation of Hydrogen Sulfide and Nrf2 Activation.D-半胱氨酸通过生成硫化氢和激活 Nrf2 激活小脑浦肯野细胞中的伴侣介导的自噬。
Cells. 2022 Apr 5;11(7):1230. doi: 10.3390/cells11071230.
2
d-Cysteine promotes dendritic development in primary cultured cerebellar Purkinje cells via hydrogen sulfide production.d-半胱氨酸通过产生硫化氢促进原代培养小脑浦肯野细胞的树突发育。
Mol Cell Neurosci. 2018 Dec;93:36-47. doi: 10.1016/j.mcn.2018.10.002. Epub 2018 Oct 19.
3
Identification of a novel aromatic-turmerone analog that activates chaperone-mediated autophagy through the persistent activation of p38.一种通过持续激活p38来激活伴侣介导的自噬的新型芳基姜黄酮类似物的鉴定。
Front Cell Dev Biol. 2024 Aug 8;12:1418296. doi: 10.3389/fcell.2024.1418296. eCollection 2024.
4
Ataxic phenotype and neurodegeneration are triggered by the impairment of chaperone-mediated autophagy in cerebellar neurons.伴侣蛋白介导的自噬在小脑神经元中受损会引发共济失调表型和神经退行性变。
Neuropathol Appl Neurobiol. 2021 Feb;47(2):198-209. doi: 10.1111/nan.12649. Epub 2020 Aug 9.
5
Chaperone-mediated autophagy degrades Keap1 and promotes Nrf2-mediated antioxidative response.伴侣蛋白介导的自噬降解 Keap1 并促进 Nrf2 介导的抗氧化反应。
Aging Cell. 2022 Jun;21(6):e13616. doi: 10.1111/acel.13616. Epub 2022 May 10.
6
Transcription factor NFE2L2/NRF2 modulates chaperone-mediated autophagy through the regulation of LAMP2A.转录因子 NFE2L2/NRF2 通过调节 LAMP2A 来调节伴侣介导的自噬。
Autophagy. 2018;14(8):1310-1322. doi: 10.1080/15548627.2018.1474992. Epub 2018 Jul 26.
7
[Availability of D-cysteine as a protectant for cerebellar neurons].[D-半胱氨酸作为小脑神经元保护剂的可用性]
Nihon Yakurigaku Zasshi. 2019;154(3):133-137. doi: 10.1254/fpj.154.133.
8
Chaperone-Mediated Autophagy Suppresses Apoptosis via Regulation of the Unfolded Protein Response during Chronic Obstructive Pulmonary Disease Pathogenesis.伴侣蛋白介导的自噬通过调节慢性阻塞性肺疾病发病过程中的未折叠蛋白反应来抑制细胞凋亡。
J Immunol. 2020 Sep 1;205(5):1256-1267. doi: 10.4049/jimmunol.2000132. Epub 2020 Jul 22.
9
Therapeutic potential of d-cysteine against in vitro and in vivo models of spinocerebellar ataxia.D-半胱氨酸对脊髓小脑共济失调体外和体内模型的治疗潜力。
Exp Neurol. 2021 Sep;343:113791. doi: 10.1016/j.expneurol.2021.113791. Epub 2021 Jun 19.
10
Sodium Sulfide Attenuates Ischemic-Induced Heart Failure by Enhancing Proteasomal Function in an Nrf2-Dependent Manner.硫化钠通过以Nrf2依赖的方式增强蛋白酶体功能减轻缺血诱导的心力衰竭。
Circ Heart Fail. 2016 Apr;9(4):e002368. doi: 10.1161/CIRCHEARTFAILURE.115.002368.

引用本文的文献

1
Biological and Analytical Perspectives on D-Amino Acids in Cancer Diagnosis and Therapy.癌症诊断与治疗中D-氨基酸的生物学与分析视角
Pharmaceuticals (Basel). 2025 May 9;18(5):705. doi: 10.3390/ph18050705.
2
d-amino acids: new functional insights.D-氨基酸：新的功能见解
FEBS J. 2025 Sep;292(17):4395-4417. doi: 10.1111/febs.70083. Epub 2025 Mar 27.
3
Distribution and functional significance of KLF15 in mouse cerebellum.KLF15在小鼠小脑中的分布及功能意义

本文引用的文献

1
New Insights into the Mechanisms of Chaperon-Mediated Autophagy and Implications for Kidney Diseases.伴侣蛋白介导的自噬机制的新见解及其对肾脏疾病的影响。
Cells. 2022 Jan 25;11(3):406. doi: 10.3390/cells11030406.
2
D-cysteine is an endogenous regulator of neural progenitor cell dynamics in the mammalian brain.D-半胱氨酸是哺乳动物大脑神经祖细胞动态的内源性调节剂。
Proc Natl Acad Sci U S A. 2021 Sep 28;118(39). doi: 10.1073/pnas.2110610118.
3
The myristoylated alanine-rich C-kinase substrates (MARCKS): A membrane-anchored mediator of the cell function.
Mol Brain. 2025 Jan 21;18(1):3. doi: 10.1186/s13041-025-01172-3.
4
Identification of a novel aromatic-turmerone analog that activates chaperone-mediated autophagy through the persistent activation of p38.一种通过持续激活p38来激活伴侣介导的自噬的新型芳基姜黄酮类似物的鉴定。
Front Cell Dev Biol. 2024 Aug 8;12:1418296. doi: 10.3389/fcell.2024.1418296. eCollection 2024.
豆蔻酰化的丙氨酸丰富的 C 激酶底物 (MARCKS)：一种细胞膜锚定的细胞功能介质。
Autoimmun Rev. 2021 Nov;20(11):102942. doi: 10.1016/j.autrev.2021.102942. Epub 2021 Sep 10.
4
Hydrogen sulphide attenuates neuronal apoptosis of substantia nigra by re-establishing autophagic flux via promoting leptin signalling in a 6-hydroxydopamine rat model of Parkinson's disease.在6-羟基多巴胺诱导的帕金森病大鼠模型中，硫化氢通过促进瘦素信号通路重建自噬流，从而减轻黑质神经元凋亡。
Clin Exp Pharmacol Physiol. 2022 Jan;49(1):122-133. doi: 10.1111/1440-1681.13587. Epub 2021 Sep 22.
5
Metformin activates chaperone-mediated autophagy and improves disease pathologies in an Alzheimer disease mouse model.二甲双胍激活伴侣介导的自噬并改善阿尔茨海默病小鼠模型中的疾病病理。
Protein Cell. 2021 Oct;12(10):769-787. doi: 10.1007/s13238-021-00858-3. Epub 2021 Jul 21.
6
Hydrogen Sulfide (HS) and Polysulfide (HS) Signaling: The First 25 Years.硫化氢（HS）和多硫化物（HS）信号转导：前 25 年。
Biomolecules. 2021 Jun 16;11(6):896. doi: 10.3390/biom11060896.
7
Therapeutic potential of d-cysteine against in vitro and in vivo models of spinocerebellar ataxia.D-半胱氨酸对脊髓小脑共济失调体外和体内模型的治疗潜力。
Exp Neurol. 2021 Sep;343:113791. doi: 10.1016/j.expneurol.2021.113791. Epub 2021 Jun 19.
8
Aromatic-Turmerone Analogs Protect Dopaminergic Neurons in Midbrain Slice Cultures through Their Neuroprotective Activities.芳香姜黄酮类似物通过其神经保护活性保护中脑切片培养物中的多巴胺能神经元。
Cells. 2021 May 3;10(5):1090. doi: 10.3390/cells10051090.
9
Chaperone-mediated autophagy prevents collapse of the neuronal metastable proteome.伴侣蛋白介导的自噬可防止神经元亚稳态蛋白质组的崩溃。
Cell. 2021 May 13;184(10):2696-2714.e25. doi: 10.1016/j.cell.2021.03.048. Epub 2021 Apr 22.
10
Autophagy in Human Diseases.人类疾病中的自噬
N Engl J Med. 2020 Oct 15;383(16):1564-1576. doi: 10.1056/NEJMra2022774.