A plausible involvement of plasmalemmal voltage‐dependent anion channel 1 in the neurotoxicity of 15‐deoxy‐Δ 12,14 ‐prostaglandin J 2

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 .