scholarly journals The Impact of Paeoniflorin onα-Synuclein Degradation Pathway

2015 ◽  
Vol 2015 ◽  
pp. 1-8
Author(s):  
Zenglin Cai ◽  
Xinzhi Zhang ◽  
Yongjin Zhang ◽  
Xiuming Li ◽  
Jing Xu ◽  
...  
Keyword(s):  
Chinese Medicine ◽  
Traditional Chinese Medicine ◽  
Fluorescence Intensity ◽  
Cell Damage ◽  
Degradation Pathway ◽  
Ubiquitin Proteasome Pathway ◽  
Pathway Expression ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
The Impact

Paeoniflorin (PF) is the major active ingredient in the traditional Chinese medicine Radix. It plays a neuroprotective role by regulating autophagy and the ubiquitin-proteasome degradation pathway. In this study, we found PF significantly reduced cell damage caused by MPP+, returning cells to normal state. Cell viability significantly improved after 24 h exposure to RAPA and PF in the MPP+ group (allP<0.01). CAT and SOD activities were significantly decreased after PF and RAPA treatment, compared with MPP+ (P<0.001). In addition, MPP+ activated both LC3-II and E1; RAPA increased LC3-II but inhibited E1. PF significantly upregulated both LC3-II (autophagy) and E1 (ubiquitin-proteasome pathway) expression (P<0.001), promoted degradation ofα-synuclein, and reduced cell damage. We show MPP+ enhanced immunofluorescence signal of intracellularα-synuclein and LC3. Fluorescence intensity ofα-synuclein decreased after PF treatment. In conclusion, these data show PF reversed the decline of proteasome activity caused by MPP+ and significantly upregulated both autophagy and ubiquitin-proteasome pathways, promoted the degradation ofα-synuclein, and reduced cell damage. These findings suggest PF is a potential therapeutic medicine for neurodegenerative diseases.

The ubiquitin–proteasome pathway in viral infectionsThis paper is one of a selection of papers published in this Special Issue, entitled Young Investigator's Forum.

2006 ◽  
Vol 84 (1) ◽  
pp. 5-14 ◽  
Author(s):  
Guang Gao ◽  
Honglin Luo
Keyword(s):  
Critical Role ◽  
Proteasome Inhibition ◽  
Degradation Pathway ◽  
Enteroviral Infection ◽  
Ubiquitin Proteasome Pathway ◽  
Potential Therapeutic Application ◽  
Intracellular Protein Degradation ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway ◽  
And Function

The cellular biological function of the ubiquitin–proteasome pathway as a major intracellular protein degradation pathway, and as an important modulator for the regulation of many fundamental cellular processes has been greatly appreciated over the last decade. The critical role of the ubiquitin–proteasome pathway in viral pathogenesis has become increasingly apparent. Many viruses have been reported to evolve different strategies to utilize the ubiquitin–proteasome pathway for their own benefits. Here, we review the general background and function of the ubiquitin–proteasome pathway, summarize our current understanding of how viruses use this pathway to target cellular proteins, and finally, discuss the roles of this pathway in enteroviral infection, and the potential therapeutic application of proteasome inhibition in myocarditis.

scholarly journals Regulation of Bovine Papillomavirus Replicative Helicase E1 by the Ubiquitin-Proteasome Pathway

2002 ◽  
Vol 76 (22) ◽  
pp. 11350-11358 ◽  
Author(s):  
Marie-Helene Malcles ◽  
Nathalie Cueille ◽  
Francisca Mechali ◽  
Olivier Coux ◽  
Catherine Bonne-Andrea
Keyword(s):  
Cyclin E ◽  
Degradation Pathway ◽  
Host Cells ◽  
Bovine Papillomavirus ◽  
Free System ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Infected Cells ◽  
Proteasome Pathway ◽  
Replication Activity

ABSTRACT Papillomaviruses maintain their genomes in a relatively constant copy number as stable extrachromosomal plasmids in the nuclei of dividing host cells. The viral initiator of replication, E1, is not detected in papillomavirus-infected cells. Here, we present evidence that E1 encoded by bovine papillomavirus type 1 is an unstable protein that is degraded through the ubiquitin-proteasome pathway. In a cell-free system derived from Xenopus egg extracts, E1 degradation is regulated by both cyclin E/Cdk2 binding and E1 replication activity. Free E1 is readily ubiquitinated and degraded by the proteasome, while it becomes resistant to this degradation pathway when bound to cyclin E/Cdk2 complexes before the start of DNA synthesis. This stabilization is reversed in a process involving E1-dependent replication activity. In transiently transfected cells, E1 is also polyubiquitinated and accumulates when proteasome activity is inhibited. Thus, the establishment and maintenance of a stable number of papillomavirus genomes in latently infected cells are in part a function of regulated ubiquitin-mediated degradation of E1.

scholarly journals Molecular Pathogenesis of Pulmonary Fibrosis, with Focus on Pathways Related to TGF-β and the Ubiquitin-Proteasome Pathway

2021 ◽  
Vol 22 (11) ◽  
pp. 6107
Author(s):  
Naoki Inui ◽  
Satoshi Sakai ◽  
Masatoshi Kitagawa
Keyword(s):  
Extracellular Matrix ◽  
Endothelial Cells ◽  
Pulmonary Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Cell Damage ◽  
Mesenchymal Transition ◽  
Ubiquitin Proteasome Pathway ◽  
Matrix Deposition ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease. During the past decade, novel pathogenic mechanisms of IPF have been elucidated that have shifted the concept of IPF from an inflammatory-driven to an epithelial-driven disease. Dysregulated repair responses induced by recurrent epithelial cell damage and excessive extracellular matrix accumulation result in pulmonary fibrosis. Although there is currently no curative therapy for IPF, two medications, pirfenidone and nintedanib, have been introduced based on understanding the pathogenesis of the disease. In this review, we discuss advances in understanding IPF pathogenesis, highlighting epithelial–mesenchymal transition (EMT), the ubiquitin-proteasome system, and endothelial cells. TGF-β is a central regulator involved in EMT and pulmonary fibrosis. HECT-, RING finger-, and U-box-type E3 ubiquitin ligases regulate TGF-β-Smad pathway-mediated EMT via the ubiquitin-proteasome pathway. p27 degradation mediated by the SCF-type E3 ligase, Skp2, contributes to the progression of pulmonary fibrosis by promotion of either mesenchymal fibroblast proliferation, EMT, or both. In addition to fibroblasts as key effector cells in myofibroblast differentiation and extracellular matrix deposition, endothelial cells also play a role in the processes of IPF. Endothelial cells can transform into myofibroblasts; therefore, endothelial–mesenchymal transition can be another source of myofibroblasts.

scholarly journals Role of ubiquitin-proteasome degradation pathway in biogenesis efficiency of β-cell ATP-sensitive potassium channels

2005 ◽  
Vol 289 (5) ◽  
pp. C1351-C1359 ◽  
Author(s):  
Fei-Fei Yan ◽  
Chia-Wei Lin ◽  
Etienne A. Cartier ◽  
Show-Ling Shyng
Keyword(s):  
Surface Expression ◽  
Degradation Pathway ◽  
Sulfonylurea Receptor ◽  
Membrane Excitability ◽  
Β Cells ◽  
Β Cell ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

ATP-sensitive potassium (KATP) channels of pancreatic β-cells mediate glucose-induced insulin secretion by linking glucose metabolism to membrane excitability. The number of plasma membrane KATP channels determines the sensitivity of β-cells to glucose stimulation. The KATP channel is formed in the endoplasmic reticulum (ER) on coassembly of four inwardly rectifying potassium channel Kir6.2 subunits and four sulfonylurea receptor 1 (SUR1) subunits. Little is known about the cellular events that govern the channel's biogenesis efficiency and expression. Recent studies have implicated the ubiquitin-proteasome pathway in modulating surface expression of several ion channels. In this work, we investigated whether the ubiquitin-proteasome pathway plays a role in the biogenesis efficiency and surface expression of KATP channels. We provide evidence that, when expressed in COS cells, both Kir6.2 and SUR1 undergo ER-associated degradation via the ubiquitin-proteasome system. Moreover, treatment of cells with proteasome inhibitors MG132 or lactacystin leads to increased surface expression of KATP channels by increasing the efficiency of channel biogenesis. Importantly, inhibition of proteasome function in a pancreatic β-cell line, INS-1, that express endogenous KATP channels also results in increased channel number at the cell surface, as assessed by surface biotinylation and whole cell patch-clamp recordings. Our results support a role of the ubiquitin-proteasome pathway in the biogenesis efficiency and surface expression of β-cell KATP channels.

The Ubiquitin-Proteasome Pathway an Emerging Anticancer Strategy for Therapeutics: A Patent Analysis

2015 ◽  
Vol 10 (2) ◽  
pp. 201-213 ◽  
Author(s):  
Chakresh Jain ◽  
Shivam Arora ◽  
Aparna Khanna ◽  
Money Gupta ◽  
Gulshan Wadhwa ◽  
...  
Keyword(s):  
Patent Analysis ◽  
Ubiquitin Proteasome Pathway ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway
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