cAMP 刺激大鼠脊髓神经元中的泛素/蛋白酶体途径。
cAMP stimulates the ubiquitin/proteasome pathway in rat spinal cord neurons.
机构信息
Department of Biological Sciences, Hunter College and Graduate Center, CUNY, New York, NY 10065, USA.
出版信息
Neurosci Lett. 2012 Oct 11;527(2):126-31. doi: 10.1016/j.neulet.2012.08.051. Epub 2012 Sep 5.
Abstract
Proteasome impairment and accumulation of ubiquitinated proteins are implicated in neurodegeneration associated with different forms of spinal cord injury. We show herein that elevating cAMP in rat spinal cord neurons increases 26S proteasome activity in a protein kinase A-dependent manner. Treating spinal cord neurons with dibutyryl-cAMP (db-cAMP) also raised the levels of various components of the UPP including proteasome subunits Rpt6 and β5, polyubiquitin shuttling factor p62/sequestosome1, E3 ligase CHIP, AAA-ATPase p97 and the ubiquitin gene ubB. Finally, db-cAMP reduced the accumulation of ubiquitinated proteins, proteasome inhibition, and neurotoxicity triggered by the endogenous product of inflammation prostaglandin J2. We propose that optimizing the effects of cAMP/PKA-signaling on the UPP could offer an effective therapeutic approach to prevent UPP-related proteotoxicity in spinal cord neurons.
摘要
蛋白酶体功能障碍和泛素化蛋白的积累与不同形式的脊髓损伤相关的神经退行性变有关。我们在此表明，在大鼠脊髓神经元中升高 cAMP 可通过蛋白激酶 A 依赖性方式增加 26S 蛋白酶体的活性。用二丁酰环腺苷酸 (db-cAMP) 处理脊髓神经元也提高了 UPP 的各种成分的水平，包括蛋白酶体亚基 Rpt6 和 β5、泛素穿梭因子 p62/自噬体 1、E3 连接酶 CHIP、AAA-ATP 酶 p97 和泛素基因 ubB。最后，db-cAMP 减少了由炎症内源性产物前列腺素 J2 触发的泛素化蛋白、蛋白酶体抑制和神经毒性的积累。我们提出，优化 cAMP/PKA 信号对 UPP 的影响可能为预防脊髓神经元中 UPP 相关蛋白毒性提供一种有效的治疗方法。
相似文献
1
cAMP stimulates the ubiquitin/proteasome pathway in rat spinal cord neurons.cAMP 刺激大鼠脊髓神经元中的泛素/蛋白酶体途径。
Neurosci Lett. 2012 Oct 11;527(2):126-31. doi: 10.1016/j.neulet.2012.08.051. Epub 2012 Sep 5.
2
Coordination between proteasome impairment and caspase activation leading to TAU pathology: neuroprotection by cAMP.泛素蛋白酶体功能障碍与半胱天冬酶激活导致 TAU 病理之间的协调作用：cAMP 的神经保护作用。
Cell Death Dis. 2012 Jun 21;3(6):e326. doi: 10.1038/cddis.2012.70.
3
Delta12-Prostaglandin J2 inhibits the ubiquitin hydrolase UCH-L1 and elicits ubiquitin-protein aggregation without proteasome inhibition.Δ12-前列腺素J2抑制泛素水解酶UCH-L1并引发泛素-蛋白质聚集，而不抑制蛋白酶体。
Biochem Biophys Res Commun. 2004 Jul 9;319(4):1171-80. doi: 10.1016/j.bbrc.2004.05.098.
4
cAMP perturbs inter-Sertoli tight junction permeability barrier in vitro via its effect on proteasome-sensitive ubiquitination of occludin.环磷酸腺苷（cAMP）通过影响封闭蛋白对蛋白酶体敏感的泛素化作用，在体外扰乱睾丸支持细胞间紧密连接的通透性屏障。
J Cell Physiol. 2005 Jun;203(3):564-72. doi: 10.1002/jcp.20254.
5
Protein kinase A regulates the sensitivity of spinal commissural axon turning to netrin-1 but does not switch between chemoattraction and chemorepulsion.蛋白激酶A调节脊髓连合轴突转向netrin-1的敏感性，但不会在化学吸引和化学排斥之间转换。
J Neurosci. 2006 Mar 1;26(9):2419-23. doi: 10.1523/JNEUROSCI.5419-05.2006.
6
cAMP-PKA signaling is involved in regulation of spinal HCN channels function in diabetic neuropathic pain.环腺苷酸-蛋白激酶 A 信号通路参与调节糖尿病神经病理性疼痛中海马通道功能。
Neurosci Lett. 2021 Apr 17;750:135763. doi: 10.1016/j.neulet.2021.135763. Epub 2021 Feb 19.
7
cAMP-dependent protein kinase regulates ubiquitin-proteasome-mediated degradation and subcellular localization of the nuclear receptor coactivator GRIP1.环磷酸腺苷（cAMP）依赖性蛋白激酶调节泛素-蛋白酶体介导的核受体共激活因子GRIP1的降解及亚细胞定位。
J Biol Chem. 2004 Nov 19;279(47):49120-30. doi: 10.1074/jbc.M409746200. Epub 2004 Sep 3.
8
Differential modulation of evoked and spontaneous glycine release from rat spinal cord glycinergic terminals by the cyclic AMP/protein kinase A transduction cascade.环磷酸腺苷/蛋白激酶A转导级联对大鼠脊髓甘氨酸能终末诱发和自发性甘氨酸释放的差异性调节
J Neurochem. 2004 Nov;91(3):657-66. doi: 10.1111/j.1471-4159.2004.02741.x.
9
Cyclic AMP regulates the expression of neurokinin1 receptors by neonatal rat spinal neurons in culture.
J Neurochem. 1999 Jul;73(1):50-8. doi: 10.1046/j.1471-4159.1999.0730050.x.
10
Analysis of the Protein Kinase A-Regulated Proteome of Cryptococcus neoformans Identifies a Role for the Ubiquitin-Proteasome Pathway in Capsule Formation.新型隐球菌蛋白激酶A调控蛋白质组分析确定泛素-蛋白酶体途径在荚膜形成中的作用。
mBio. 2016 Jan 12;7(1):e01862-15. doi: 10.1128/mBio.01862-15.
引用本文的文献
1
Boosting Brain Clean-Up: Can Targeting UPS Genes Offer Neuroprotection?增强大脑清理能力：靶向泛素蛋白酶体系统基因能否提供神经保护？
Mol Neurobiol. 2025 Aug 16. doi: 10.1007/s12035-025-05263-z.
2
Occupancy of the HbYX hydrophobic pocket is sufficient to induce gate opening in the archaeal 20S proteasomes.血红蛋白（HbYX）疏水口袋的占据足以诱导古细菌20S蛋白酶体的门打开。
Elife. 2025 Aug 14;14:RP106611. doi: 10.7554/eLife.106611.
3
Activators of the 26S proteasome when protein degradation increases.当蛋白质降解增加时，26S蛋白酶体的激活剂。
Exp Mol Med. 2025 Feb;57(1):41-49. doi: 10.1038/s12276-024-01385-x. Epub 2025 Jan 8.
4
Promoting proteostasis by cAMP/PKA and cGMP/PKG.通过环磷酸腺苷/蛋白激酶A和环磷酸鸟苷/蛋白激酶G促进蛋白质稳态。
Trends Mol Med. 2025 Mar;31(3):224-239. doi: 10.1016/j.molmed.2024.10.006. Epub 2024 Oct 29.
5
Occupancy of the HbYX hydrophobic pocket is sufficient to induce gate opening in the archaeal 20S proteasomes.血红蛋白（HbYX）疏水口袋的占据足以诱导古细菌20S蛋白酶体的门打开。
bioRxiv. 2025 Feb 25:2024.05.21.595185. doi: 10.1101/2024.05.21.595185.
6
Unraveling the mechanistic interplay of mediators orchestrating the neuroprotective potential of harmine.揭示介导物在调控哈林生物碱神经保护潜能中的机制相互作用。
Pharmacol Rep. 2024 Aug;76(4):665-678. doi: 10.1007/s43440-024-00602-8. Epub 2024 May 17.
7
PKR Protects the Major Catalytic Subunit of PKA Cpk1 from FgBlm10-Mediated Proteasome Degradation in .PKR 保护 PKA 的主要催化亚基 Cpk1 免受 FgBlm10 介导的蛋白酶体降解。
Int J Mol Sci. 2022 Sep 6;23(18):10208. doi: 10.3390/ijms231810208.
8
A Putative Role for Ubiquitin-Proteasome Signaling in Estrogenic Memory Regulation.泛素-蛋白酶体信号在雌激素记忆调节中的假定作用
Front Behav Neurosci. 2022 Jan 25;15:807215. doi: 10.3389/fnbeh.2021.807215. eCollection 2021.
9
Mechanisms That Activate 26S Proteasomes and Enhance Protein Degradation.激活 26S 蛋白酶体并增强蛋白质降解的机制。
Biomolecules. 2021 May 22;11(6):779. doi: 10.3390/biom11060779.
10
Expanding the role of proteasome homeostasis in Parkinson's disease: beyond protein breakdown.拓展蛋白酶体动态平衡在帕金森病中的作用：超越蛋白质降解。
Cell Death Dis. 2021 Feb 4;12(2):154. doi: 10.1038/s41419-021-03441-0.
本文引用的文献
1
Assessment of proteasome impairment and accumulation/aggregation of ubiquitinated proteins in neuronal cultures.神经元培养物中蛋白酶体损伤以及泛素化蛋白积累/聚集的评估。
Methods Mol Biol. 2011;793:273-96. doi: 10.1007/978-1-61779-328-8_18.
2
Diagnosis, pathogenesis and therapeutic targets in amyotrophic lateral sclerosis.肌萎缩侧索硬化症的诊断、发病机制和治疗靶点。
CNS Neurol Disord Drug Targets. 2010 Dec;9(6):764-78. doi: 10.2174/187152710793237502.
3
Selective degradation of p62 by autophagy.自噬选择性降解 p62。
Semin Immunopathol. 2010 Dec;32(4):431-6. doi: 10.1007/s00281-010-0220-1. Epub 2010 Sep 3.
4
Differential regulation of proteasome function in isoproterenol-induced cardiac hypertrophy.异丙肾上腺素诱导的心肌肥厚中蛋白酶体功能的差异调节。
Circ Res. 2010 Oct 29;107(9):1094-101. doi: 10.1161/CIRCRESAHA.110.222364. Epub 2010 Sep 2.
5
Selective vulnerability of neurons to acute toxicity after proteasome inhibitor treatment: implications for oxidative stress and insolubility of newly synthesized proteins.蛋白酶体抑制剂治疗后神经元对急性毒性的选择性易损性：氧化应激和新合成蛋白质的不溶性的影响。
Free Radic Biol Med. 2010 Nov 1;49(8):1290-7. doi: 10.1016/j.freeradbiomed.2010.07.014. Epub 2010 Aug 1.
6
Ubiquitin/proteasome pathway impairment in neurodegeneration: therapeutic implications.泛素/蛋白酶体通路在神经退行性变中的障碍：治疗意义。
Apoptosis. 2010 Nov;15(11):1292-311. doi: 10.1007/s10495-010-0466-z.
7
The Tor and cAMP-dependent protein kinase signaling pathways coordinately control autophagy in Saccharomyces cerevisiae.Tor 和 cAMP 依赖的蛋白激酶信号通路协同调控酿酒酵母中的自噬。
Autophagy. 2010 Feb;6(2):294-5. doi: 10.4161/auto.6.2.11129. Epub 2010 Feb 6.
8
Functional alterations of cardiac proteasomes under physiological and pathological conditions.心脏蛋白酶体在生理和病理条件下的功能改变。
Cardiovasc Res. 2010 Jan 15;85(2):339-46. doi: 10.1093/cvr/cvp282. Epub 2009 Aug 14.
9
Oxidative damage to the promoter region of SQSTM1/p62 is common to neurodegenerative disease.SQSTM1/p62启动子区域的氧化损伤在神经退行性疾病中很常见。
Neurobiol Dis. 2009 Aug;35(2):302-10. doi: 10.1016/j.nbd.2009.05.015. Epub 2009 May 28.
10
PKA rapidly enhances proteasome assembly and activity in in vivo canine hearts.蛋白激酶A迅速增强犬类活体心脏中的蛋白酶体组装及活性。
J Mol Cell Cardiol. 2009 Apr;46(4):452-62. doi: 10.1016/j.yjmcc.2008.11.001. Epub 2008 Nov 13.
Zotero 插件