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

Abstract

Introduction: 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-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.