Pyridoxal-5'-phosphate phosphatase/chronophin induces astroglial apoptosis via actin-depolymerizing factor/cofilin system in the rat brain following status epilepticus

Actin-depolymerizing factor (ADF)/colin is a small cytos-keletal protein that is a stimulus-responsive mediator of actin dynamics. ADF/colin also translocates into mito-chondria and nuclei in response to apoptotic stimuli for cytochrome c release. These ADF/colin translocations are negatively regulated by phosphorylation. Recently, it has been reported that pyridoxal-5'-phosphate (PLP) phospha-tase/chronophin (PLPP/CIN) regulates phosphorylation of ADF/colin levels. Therefore, we investigated whether PLPP/CIN contributes to apoptosis-like events via modu-lation of ADF/colin phosphorylation following status epilepticus (SE). In the present study, apoptosis-like astro-glial damages were detected in the dentate gyrus after SE. Upregulation of ADF/colin and PLPP/CIN expression in the cytoplasm and nucleus were accompanied by apoptosis-like events. PLPP/CIN level showed a direct proportionality to nuclear translocation of ADF/colin. Moreover, nuclear accumulation of apoptosis-inducing factor was simultane-ously observed with that of ADF/colin. Tat-PLPP/CIN pre-treatment accelerated astroglial apoptosis-like degeneration following SE, although Tat-PLPP/CIN transduction alone could not induce apoptosis or necrosis in astrocytes. There-fore, our ndings suggest that nuclear accumulation of ADF/colin itself may not induce apoptogenic events, but may play a synergic role in apoptosis-like astroglial loss following SE.