A plausible involvement of plasmalemmal voltage-dependent anion channel 1 in the neurotoxicity of 15-deoxy-Δ -prostaglandin J.

INTRODUCTION

15-deoxy-Δ -prostaglandin J (15d-PGJ ) 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-PGJ . In the present study, we ascertained whether membrane targets beside CRTH2 were involved in the neurotoxicity of 15d-PGJ .

METHODS

Neuronal membrane targets for 15d-PGJ 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-PGJ . Modification of VDAC1 with 15d-PGJ 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-PGJ . The anti-VDAC antibody significantly attenuated the neurotoxicity of 15d-PGJ , accompanied by the suppression of the 15d-PGJ -stimulated caspase-3.

CONCLUSION

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