15-Deoxy-Δ12,14-prostaglandin J2 as an electrophilic mediator

Shibata, Takahiro

doi:10.1080/09168451.2015.1012149

Cited by 28 publications

(21 citation statements)

References 53 publications

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“…Indeed, 15d-PGJ 2 induces differentiation of rat embryonic midbrain cells into dopaminergic neuronal cells in a PPARγ-dependent manner [25]. Nevertheless, 15d-PGJ 2 is also involved in PPARγ-independent pathways via direct covalent binding to proteins other than PPARγ [47]; 15d-PGJ 2 enhances nerve growth factor-induced neurite outgrowth via covalent binding to activator protein-1 [48] or the transient receptor potential vanilloid 1 [49] in PC12 cells. These studies suggest that 15d-PGJ 2 -induced neuritogenesis and neuronal differentiation involve pathways that are dependent or independent of PPARγ, according to the cell type.…”

Section: Discussionmentioning

confidence: 99%

The Molecular Mechanisms Underlying Prostaglandin D2-Induced Neuritogenesis in Motor Neuron-Like NSC-34 Cells

Nango

Kosuge

Yoshimura

et al. 2020

Cells

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Prostaglandins are a group of physiologically active lipid compounds derived from arachidonic acid. Our previous study has found that prostaglandin E2 promotes neurite outgrowth in NSC-34 cells, which are a model for motor neuron development. However, the effects of other prostaglandins on neuronal differentiation are poorly understood. The present study investigated the effect of prostaglandin D2 (PGD2) on neuritogenesis in NSC-34 cells. Exposure to PGD2 resulted in increased percentages of neurite-bearing cells and neurite length. Although D-prostanoid receptor (DP) 1 and DP2 were dominantly expressed in the cells, BW245C (a DP1 agonist) and 15(R)-15-methyl PGD2 (a DP2 agonist) had no effect on neurite outgrowth. Enzyme-linked immunosorbent assay demonstrated that PGD2 was converted to 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) under cell-free conditions. Exogenously applied 15d-PGJ2 mimicked the effect of PGD2 on neurite outgrowth. GW9662, a peroxisome proliferator-activated receptor–gamma (PPARγ) antagonist, suppressed PGD2-induced neurite outgrowth. Moreover, PGD2 and 15d-PGJ2 increased the protein expression of Islet-1 (the earliest marker of developing motor neurons), and these increases were suppressed by co-treatment with GW9662. These results suggest that PGD2 induces neuritogenesis in NSC-34 cells and that PGD2-induced neurite outgrowth was mediated by the activation of PPARγ through the metabolite 15d-PGJ2.

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Section: Discussionmentioning

confidence: 99%

The Molecular Mechanisms Underlying Prostaglandin D2-Induced Neuritogenesis in Motor Neuron-Like NSC-34 Cells

Nango

Kosuge

Yoshimura

et al. 2020

Cells

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“…PGD2 has a relatively short half-life, after which it is further converted to various bioactive derivatives (Schuligoi et al, 2007;Shibata et al, 2002). Induction of ROS by PGD2 treatment may be attributed to 15-deoxy-delta-12,14-prostaglandin J2 (15d-PGJ2), a spontaneous electrophilic metabolite of PGD2 that has been shown to mediate some of its biological actions via ROS (Shibata, 2015;Wang and Mak, 2011). In addition to PGD2,15d-PGJ2 has been also found to be elevated in bald scalp, and its inhibitory effects on hair growth were more profound compared with the parental prostaglandin (Garza et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin D2 Uses Components of ROS Signaling to Enhance Testosterone Production in Keratinocytes

Mantel

McDonald

Goldsborough

et al. 2017

Journal of Investigative Dermatology Symposium Proceedings

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Elevated levels of prostaglandin D2 (PGD2) have been shown to be present in the bald scalp of androgenic alopecia (AGA) patients and to functionally inhibit hair growth. However, its precise mechanism in AGA has yet to be clearly defined. Although testosterone plays a critical role in the initiation and progression of AGA, the existence of a possible link between PGD2 and testosterone in skin has not been investigated. Here we show that human keratinocytes treated with PGD2 show enhanced capacity to convert the weak androgen, androstenedione, to testosterone. At the same time, treatment with PGD2 induced reactive oxygen species as indicated by generation of the lipid peroxidation product, 4-hydroxynonenal. To determine whether these two events are linked, we used the reactive oxygen species scavenger N-acetyl-cysteine, which blocked the enhanced testosterone production from PGD2-treated keratinocytes. Our study suggests the existence of a possible crosstalk between the PGD2-reactive oxygen species axis and testosterone metabolism in keratinocytes. Thus, we propose that AGA patients might benefit from the use of N-acetyl-cysteine or other antioxidants as a supplement to currently available or emerging AGA therapies such as finasteride, minoxidil, and PGD2 receptor blockers.

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“…in several cell and potentially acts as an endogenous suppressor of inflammation (29, 30). There are a number of possible mechanisms for this activity (31). First, 15d-PGJ 2 is a ligand for peroxisome proliferator-activated receptor gamma (PPAR-γ), a member of the nuclear receptor superfamily and a transcription factor with pleiotropic effects on adipocyte differentiation, glucose homeostasis, lipid metabolism, cell growth, and inflammation (29, 32).…”

Section: Discussionmentioning

confidence: 99%

“…One of these products, PGD 2 , is an abundant prostaglandin in several tissues. PGD 2 activates G-protein-coupled receptors on its target cells, but PGD 2 also undergoes dehydration in vivo and in vitro to generate cyclopentenone metabolites of the J series, including 15-deoxy-delta 12,14 -prostaglandin J 2 (15d-PGJ 2 ) (2, 3). 15d-PGJ 2 represses inflammatory responses in several models, including modulation of genes such as iNOS, TNF-α, and COX-2 (4, 5).…”

Section: Introductionmentioning

confidence: 99%

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

2016

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15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is an electrophilic lipid mediator derived from PGD2 with potent anti-inflammatory effects. These are likely to be due to the covalent modification of cellular proteins, via a reactive α,β-unsaturated carbonyl group in its cyclopentenone ring. This study was carried out to identify novel cellular target(s) for covalent modification by 15d-PGJ2 and to investigate the anti-inflammatory effects of the prostaglandin on endothelial cells (EC). The data presented here show that 15d-PGJ2 modifies and inhibits components of the proteasome and consequently inhibits the activation of the NF-κB pathway in response to TNF-α. This, in turn, inhibits the adhesion and migration of monocytes toward activated EC, by reducing the expression of adhesion molecules and chemokines in the EC. The effects are consistent with the covalent modification of 13 proteins in the 19S particle of the proteasome identified by mass spectrometry and the suppression of proteasome function, and were similar to the effects seen with a known proteasome inhibitor (MG132). The ubiquitin–proteasome system has been implicated in the regulation of several inflammatory processes and the observation that 15d-PGJ2 profoundly affects the proteasome functions in human EC suggests that 15d-PGJ2 may regulate the progression of inflammatory disorders such as atherosclerosis.

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15-Deoxy-Δ12,14-prostaglandin J2 as an electrophilic mediator

Cited by 28 publications

References 53 publications

The Molecular Mechanisms Underlying Prostaglandin D2-Induced Neuritogenesis in Motor Neuron-Like NSC-34 Cells

The Molecular Mechanisms Underlying Prostaglandin D2-Induced Neuritogenesis in Motor Neuron-Like NSC-34 Cells

Prostaglandin D2 Uses Components of ROS Signaling to Enhance Testosterone Production in Keratinocytes

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

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