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KMID : 0606920130210030222
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Biomolecules & Therapeutics
2013 Volume.21 No. 3 p.222 ~ p.228
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Valproic Acid Regulates α-Synuclein Expression through JNK Pathway in Rat Primary Astrocytes
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Kim Jung-Nam
Kim Min-Kyeong
Cho Kyu-Suk
Choi Chang-Soon
Park Seung-Hwa
Yang Sung-IL
Joo So-Hyun
Park Jin-Hee
Bahn Geon-Ho
Shin Chan-Young
Lee He-Jin
Han Seol-Heui
Kwon Kyoung-Ja
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Abstract
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Although the role of α-synuclein aggregation on Parkinson’s disease is relatively well known, the physiological role and the regulatory mechanism governing the expression of α-synuclein are unclear yet. We recently reported that α-synuclein is expressed and secreted from cultured astrocytes. In this study, we investigated the effect of valproic acid (VPA), which has been suggested to provide neuroprotection by increasing α-synuclein in neuron, on α-synuclein expression in rat primary astrocytes. VPA concentrationdependently increased the protein expression level of α-synuclein in cultured rat primary astrocytes with concomitant increase in mRNA expression level. Likewise, the level of secreted α-synuclein was also increased by VPA. VPA increased the phosphorylation of Erk1/2 and JNK and pretreatment of a JNK inhibitor SP600125 prevented the VPA-induced increase in α-synuclein. Whether the increased α-synuclein in astrocytes is involved in the reported neuroprotective effects of VPA awaits further investigation.
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KEYWORD
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α-synuclein, Valproic acid, Stability, JNK, Neuroprotection, Acetylation
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