Potential role of pyridoxal-5′-phosphate phosphatase/chronopin in epilepsy

• Published in: Experimental neurology Vol. 211; no. 1; pp. 128 - 140
• Main Authors: Kim, Ji-Eun, Kim, Dae-Won, Kwak, Sung-Eun, Kwon, Oh-Shin, Choi, Soo-Young, Kang, Tae-Cheon
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.05.2008; Elsevier
• Subjects: Actin Cytoskeleton - metabolism; Actin Depolymerizing Factors - metabolism; Actin dynamics; Actin-depolymerizing factor (ADF)/cofilin; Animals; Biological and medical sciences; Cloning, Molecular; Disease Models, Animal; Electric Stimulation; Epilepsy; Evoked Potentials - drug effects; Evoked Potentials - radiation effects; Gene Expression Regulation - drug effects; Gene Expression Regulation - physiology; Glial Fibrillary Acidic Protein - metabolism; Headache. Facial pains. Syncopes. Epilepsia. Intracranial hypertension. Brain oedema. Cerebral palsy; Hippocampus - drug effects; Hippocampus - metabolism; Hippocampus - physiopathology; Male; Medical sciences; Microfilament Proteins - metabolism; Nervous system (semeiology, syndromes); Neurology; Phosphopyruvate Hydratase - metabolism; Phosphoric Monoester Hydrolases - genetics; Phosphoric Monoester Hydrolases - metabolism; Pilocarpine; Pyridoxal-5′-phosphate (PLP)-phosphatase/chronophin; Pyridoxine - pharmacology; Rats; Rats, Sprague-Dawley; Receptor-Interacting Protein Serine-Threonine Kinases - metabolism; Receptors, Purinergic P2 - metabolism; Receptors, Purinergic P2X7; src Homology Domains; Status Epilepticus - chemically induced; Status Epilepticus - metabolism; Status Epilepticus - pathology; Status Epilepticus - physiopathology; Vitamin B 6 metabolism; Vitamin B Complex - pharmacology; Pyridoxal-5′-phosphate (PLP)-phosphatase/chronophin; Actin-depolymerizing factor (ADF)/cofilin; Vitamin B 6 metabolism; Epilepsy; Actin dynamics; Nervous system diseases; Enzyme; Vitamin; Phosphoric monoester hydrolases; Esterases; Metabolism; Cerebral disorder; Pyridoxal-5'-phosphate (PLP)-phosphatase/chronophin; Pyridoxal phosphate; Vitamin B6 metabolism; Central nervous system disease; Hydrolases
• ISSN: 0014-4886; 1090-2430
• DOI: 10.1016/j.expneurol.2008.01.029

Changes in actin dynamics and pyridoxal-5′-phosphate (PLP) metabolisms are closely related to the pathophysiological profiles of the epileptic hippocampus. Recently, it has been reported that PLP phosphatase/chronophin (PLPP/CIN) directly dephosphorylates actin-depolymerizing factor (ADF)/cofilin as well as PLP. In the present study, therefore, we have investigated whether PLPP/CIN is linked to the dynamics of actin filament assembly and the excitability in the rat hippocampus. In control animals, pyridoxine chloride (PNP) treatment increased PLPP/CIN immunoreactivity only in astrocytes, which did not affect electrophysiological properties. Following status epilepticus, the PLPP/CIN protein level increased in granule cells and reactive astrocytes. These changes in PLPP/CIN protein level showed an inverse correlation with phospho-ADF (pADF)/cofilin levels and F-actin content. These changes were also accompanied by alterations in the excitability ratio and paired-pulse inhibition. Transduction of PLPP/CIN by Tat-PLPP/CIN showed similar effects on pADF/cofilin levels, F-actin content and excitability ratio in normal animals. These findings suggest that PLPP/CIN-mediated actin dynamics may play an important role in the changes of morphological properties and excitability of the epileptic hippocampus.