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)/cofilin is a small cytoskeletal protein that is a stimulus-responsive mediator of actin dynamics. ADF/cofilin also translocates into mitochondria and nuclei in response to apoptotic stimuli for cytochrome c release. These ADF/cofilin translocations are negatively regulated by phosphorylation. Recently, it has been reported that pyridoxal-5'-phosphate (PLP) phosphatase/chronophin (PLPP/CIN) regulates phosphorylation of ADF/cofilin levels. Therefore, we investigated whether PLPP/CIN contributes to apoptosis-like events via modulation of ADF/cofilin phosphorylation following status epilepticus (SE). In the present study, apoptosis-like astroglial damages were detected in the dentate gyrus after SE. Upregulation of ADF/cofilin 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/cofilin. Moreover, nuclear accumulation of apoptosis-inducing factor was simultaneously observed with that of ADF/cofilin. Tat-PLPP/CIN pretreatment accelerated astroglial apoptosis-like degeneration following SE, although Tat-PLPP/CIN transduction alone could not induce apoptosis or necrosis in astrocytes. Therefore, our findings suggest that nuclear accumulation of ADF/cofilin itself may not induce apoptogenic events, but may play a synergic role in apoptosis-like astroglial loss following SE.
Kim
Ji-Eun
JE
Department of Anatomy and Neurobiology, College of Medicine, Hallym University, Chunchon 200-702, South Korea.
Ryu
Hea Jin
HJ
Kim
Min-Ju
MJ
Kim
Dae-Won
DW
Kwon
Oh-Shin
OS
Choi
Soo Young
SY
Kang
Tae-Cheon
TC
D051339:Actin Depolymerizing Factors / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001253:Astrocytes / Q000201:enzymology* / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013226:Status Epilepticus / Q000378:metabolism* / Q000473:pathology*
D051339:Actin Depolymerizing Factors; C022493:pyridoxal-5-phosphatase; D010744:Phosphoric Monoester Hydrolases