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

Abstract
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.
AuthorsJi-Eun Kim, Hea Jin Ryu, Min-Ju Kim, Dae-Won Kim, Oh-Shin Kwon, Soo Young Choi, Tae-Cheon Kang
JournalGlia (Glia) Vol. 58 Issue 16 Pg. 1937-48 (Dec 2010) ISSN: 1098-1136 [Electronic] United States
PMID20737471 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Actin Depolymerizing Factors
  • pyridoxal-5-phosphatase
  • Phosphoric Monoester Hydrolases
Topics
  • Actin Depolymerizing Factors (metabolism)
  • Animals
  • Apoptosis (physiology)
  • Astrocytes (enzymology, pathology)
  • Cell Nucleus (metabolism)
  • Cytoplasm (metabolism)
  • Dentate Gyrus (metabolism, pathology)
  • Male
  • Mitochondria (metabolism)
  • Phosphoric Monoester Hydrolases (genetics, metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Status Epilepticus (metabolism, pathology)

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