Dataset Information

A plausible involvement of plasmalemmal voltage-dependent anion channel 1 in the neurotoxicity of 15-deoxy-?^12,14 -prostaglandin J₂.

ABSTRACT:

Introduction

15-deoxy-?^12,14 -prostaglandin J₂ (15d-PGJ₂ ) causes neuronal apoptosis independently of its nuclear receptor, peroxysome-proliferator activated receptor ?. Its membrane receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), did not also mediate the neurotoxicity of 15d-PGJ₂ . In the present study, we ascertained whether membrane targets beside CRTH2 were involved in the neurotoxicity of 15d-PGJ₂ .

Methods

Neuronal membrane targets for 15d-PGJ₂ were separated by two-dimensional electrophoresis, identified by proteomic approach. Their localizations were detected by microscopic immunofluorescence study. Cell viability and apoptosis was evaluated by MTT-reducing activity and caspase-3 activity, respectively.

Results

Voltage-dependent anion channel 1 (VDAC1) was identified as one of membrane targets for 15d-PGJ₂ . Modification of VDAC1 with 15d-PGJ₂ was detected by pull-down assay. VDAC1 was detected in the plasma membrane and localized on the neuronal cell surface. VDAC1 was partially colocalized with membrane targets for 15d-PGJ₂ . The anti-VDAC antibody significantly attenuated the neurotoxicity of 15d-PGJ₂ , accompanied by the suppression of the 15d-PGJ₂ -stimulated caspase-3.

Conclusion

These findings suggested that the plasmalemmal VDAC might be involved in the neurotoxicity of 15d-PGJ₂ .

SUBMITTER: Koma H

PROVIDER: S-EPMC7749624 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

A plausible involvement of plasmalemmal voltage-dependent anion channel 1 in the neurotoxicity of 15-deoxy-Δ12,14 -prostaglandin J2.

Koma Hiromi H Yamamoto Yasuhiro Y Okamura Noboru N Yagami Tatsurou T

Brain and behavior 20201116 12

<h4>Introduction</h4>15-deoxy-Δ12,14 -prostaglandin J2 (15d-PGJ2 ) causes neuronal apoptosis independently of its nuclear receptor, peroxysome-proliferator activated receptor γ. Its membrane receptor, chemoattractant receptor-homologous molecule expressed on Th2 cells (CRTH2), did not also mediate the neurotoxicity of 15d-PGJ2 . In the present study, we ascertained whether membrane targets beside CRTH2 were involved in the neurotoxicity of 15d-PGJ ...[more]

PMID: 33200588

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Project description:Background15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2), one of the major metabolites from prostaglandin D2 in arachidonic acid metabolic pathway, has potential anti-inflammatory properties. The objective of this study was to explore the effects of 15d-PGJ2-loaded poly(D,L-lactide-co-glycolide) nanocapsules (15d-PGJ2-NC) on inflammatory responses and bone regeneration in local bone defect.MethodsThe study was conducted on 96 Wistar rats from June 2014 to March 2016. Saline, unloaded nanoparticles, free 15d-PGJ2or 15d-PGJ2-NC, were delivered through a collagen vehicle inside surgically created transcortical defects in rat femurs. Interleukin-6 (IL-6), interleukin-1 beta (IL-1β), and tumor necrosis factor-alpha (TNF-α) levels in the surrounding soft tissue were analyzed by Western blot and in the defect by quantitative real-time polymerase chain reaction over 14 days. Simultaneously, bone morphogenetic protein-6 (BMP-6) and platelet-derived growth factor-B (PDGF-B) messenger RNA (mRNA) in the defect were examined. New bone formation and EphrinB2 and osteoprotegerin (OPG) protein expression in the cortical defect were observed by Masson's Trichrome staining and immunohistochemistry over 28 days. Data were analyzed by one-way analysis of variance. Least-significant difference and Dunnett's T3 methods were used with a bilateral P< 0.05.ResultsApplication of l5d-PGJ2-NC (100 μg/ml) in the local bone defect significantly decreased IL-6, IL-1β, and TNF-α mRNA and protein, compared with saline-treated controls (P < 0.05). l5d-PGJ2-NC upregulated BMP-6 and PDGF-B mRNA (P < 0.05). New bone formation was observed in the cortical defect in l5d-PGJ2-NC-treated animals from 7th day onward (P < 0.001). Expression of EphrinB2 and OPG presented early on day 3 and persisted through day 28 in 15d-PGJ2-NC group (P < 0.05).ConclusionStable l5d-PGJ2-NC complexes were prepared that could attenuate IL-6, IL-1β, and TNF-α expression, while increasing new bone formation and growth factors related to bone regeneration.

Dataset Information

A plausible involvement of plasmalemmal voltage-dependent anion channel 1 in the neurotoxicity of 15-deoxy-?^12,14 -prostaglandin J₂.

Introduction

Methods

Results

Conclusion

Publications

A plausible involvement of plasmalemmal voltage-dependent anion channel 1 in the neurotoxicity of 15-deoxy-Δ<sup>12,14</sup> -prostaglandin J<sub>2</sub>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dataset Information

A plausible involvement of plasmalemmal voltage-dependent anion channel 1 in the neurotoxicity of 15-deoxy-?12,14 -prostaglandin J2.

Introduction

Methods

Results

Conclusion

Publications

A plausible involvement of plasmalemmal voltage-dependent anion channel 1 in the neurotoxicity of 15-deoxy-Δ<sup>12,14</sup> -prostaglandin J<sub>2</sub>.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

A plausible involvement of plasmalemmal voltage-dependent anion channel 1 in the neurotoxicity of 15-deoxy-?^12,14 -prostaglandin J₂.