15-Deoxy-Δ12,14-Prostaglandin J2 Modifies Components of the Proteasome and Inhibits Inflammatory Responses in Human Endothelial Cells

Marcone, Simone; Evans, Paul; Fitzgerald, Desmond J.

doi:10.3389/fimmu.2016.00459

Cited by 17 publications

(14 citation statements)

References 52 publications

(62 reference statements)

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“…A complex interplay can also occur with the protein degradation machinery. Certain oxidative insults or other types of stress can lead to the degradation of vimentin and GFAP by activating proteases [ 179 ], although some ubiquitin ligases and subunits of the proteasome can be inhibited by lipoxidation [ 180 ], which, as stated above, would result in accumulation of damaged proteins.…”

Section: Interplay Between Ptms In Type III Ifsmentioning

confidence: 99%

Type III intermediate filaments as targets and effectors of electrophiles and oxidants

Viedma-Poyatos

Pajares

2020

Redox Biology

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Intermediate filaments (IFs) play key roles in cell mechanics, signaling and homeostasis. Their assembly and dynamics are finely regulated by posttranslational modifications. The type III IFs, vimentin, desmin, peripherin and glial fibrillary acidic protein (GFAP), are targets for diverse modifications by oxidants and electrophiles, for which their conserved cysteine residue emerges as a hot spot. Pathophysiological examples of these modifications include lipoxidation in cell senescence and rheumatoid arthritis, disulfide formation in cataracts and nitrosation in endothelial shear stress, although some oxidative modifications can also be detected under basal conditions. We previously proposed that cysteine residues of vimentin and GFAP act as sensors for oxidative and electrophilic stress, and as hinges influencing filament assembly. Accumulating evidence indicates that the structurally diverse cysteine modifications, either per se or in combination with other posttranslational modifications, elicit specific functional outcomes inducing distinct assemblies or network rearrangements, including filament stabilization, bundling or fragmentation. Cysteine-deficient mutants are protected from these alterations but show compromised cellular performance in network assembly and expansion, organelle positioning and aggresome formation, revealing the importance of this residue. Therefore, the high susceptibility to modification of the conserved cysteine of type III IFs and its cornerstone position in filament architecture sustains their role in redox sensing and integration of cellular responses. This has deep pathophysiological implications and supports the potential of this residue as a drug target.

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Section: Interplay Between Ptms In Type III Ifsmentioning

confidence: 99%

Type III intermediate filaments as targets and effectors of electrophiles and oxidants

Viedma-Poyatos

Pajares

2020

Redox Biology

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“…Therefore, the same PG can have the opposite effect depending on the activated signaling pathways [107]. Most PGs have a proinflammatory effect (for example, PGE2 and PGD2), but some of them, cyclopentenone PG (PGA2 and 15d-PGJ2) in particular, are characterized by anti-inflammatory and antioxidant properties and participate in the regulation of glucose metabolism [92].…”

Section: Natural and Synthetic Ligands Of Ppars In Asthma Therapymentioning

confidence: 99%

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

et al. 2020

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The complexity of the pathogenetic mechanisms of the development of chronic inflammation in asthma determines its heterogeneity and insufficient treatment effectiveness. Nuclear transcription factors, which include peroxisome proliferatoractivated receptors, that is, PPARs, play an important role in the regulation of initiation and resolution of the inflammatory process. The ability of PPARs to modulate not only lipid homeostasis but also the activity of the inflammatory response makes them an important pathogenetic target in asthma therapy. At present, special attention is focused on natural (polyunsaturated fatty acids (PUFAs), endocannabinoids, and eicosanoids) and synthetic (fibrates, thiazolidinediones) PPAR ligands and the study of signaling mechanisms involved in the implementation of their anti-inflammatory effects in asthma. This review summarizes current views on the structure and function of PPARs, as well as their participation in the pathogenesis of chronic inflammation in asthma. The potential use of PPAR ligands as therapeutic agents for treating asthma is under discussion.

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“…The α,β-unsaturated carbonyl group located in the cyclopentenone ring can form a covalent bond with the thiol group of cysteine residues. Treatment of human aortic endothelial cells with 15d-PGJ 2 resulted in 15d-PGJ 2 -modified 19S-subunits, e.g., RPN1, RPN2, RPN3, and RPN6, while 20S-subunits were unmodified (Marcone, 2016). Further examination showed that the ChT-L activity of the proteasome was inhibited and ubiquitin-conjugated proteins were accumulated.…”

Section: Proteasome Modulation By Post-translational Modificationsmentioning

confidence: 99%

“…15d-PGJ 2 has anti-inflammatory actions, for instance by inhibiting nuclear factor-κB (NF-κB) activation (Surh et al, 2011). A possible mechanism for 15d-PGJ 2 to suppress the NF-κB pathway is by modifying and inhibiting the proteasome, which regulates the processing of NF-κB inhibitors (Marcone, 2016). 15d-PGJ 2 treatment reduced the adhesion and migration of monocytes toward TNF-α-exposed endothelial cells, a key process in vascular inflammation, and similar effects were observed upon proteasome inhibition.…”

Section: Proteasome Modulation By Post-translational Modificationsmentioning

confidence: 99%

Regulation of Proteasome Activity by (Post-)transcriptional Mechanisms

Kors

Geijtenbeek

Reits

et al. 2019

Front. Mol. Biosci.

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Intracellular protein synthesis, folding, and degradation are tightly controlled processes to ensure proper protein homeostasis. The proteasome is responsible for the degradation of the majority of intracellular proteins, which are often targeted for degradation via polyubiquitination. However, the degradation rate of proteins is also affected by the capacity of proteasomes to recognize and degrade these substrate proteins. This capacity is regulated by a variety of proteasome modulations including (1) changes in complex composition, (2) post-translational modifications, and (3) altered transcription of proteasomal subunits and activators. Various diseases are linked to proteasome modulation and altered proteasome function. A better understanding of these modulations may offer new perspectives for therapeutic intervention. Here we present an overview of these three proteasome modulating mechanisms to give better insight into the diversity of proteasomes.

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15-Deoxy-Δ12,14-Prostaglandin J2 Modifies Components of the Proteasome and Inhibits Inflammatory Responses in Human Endothelial Cells

Cited by 17 publications

References 52 publications

Type III intermediate filaments as targets and effectors of electrophiles and oxidants

Type III intermediate filaments as targets and effectors of electrophiles and oxidants

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma

Regulation of Proteasome Activity by (Post-)transcriptional Mechanisms

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