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Mood stabilizers commonly restore staurosporine-induced increase of p53 expression and following decrease of Bcl-2 expression in SH-SY5Y cells

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Title: Mood stabilizers commonly restore staurosporine-induced increase of p53 expression and following decrease of Bcl-2 expression in SH-SY5Y cells
Authors: Song, Ning Browse this author
Boku, Shuken Browse this author →KAKEN DB
Nakagawa, Shin Browse this author →KAKEN DB
Kato, Akiko Browse this author
Toda, Hiroyuki Browse this author
Takamura, Naoki Browse this author
Omiya, Yuki Browse this author
Kitaichi, Yuji Browse this author
Inoue, Takeshi Browse this author →KAKEN DB
Koyama, Tsukasa Browse this author →KAKEN DB
Keywords: Apoptosis
Dentate gyrus
Adult neurogenesis
Issue Date: 7-Aug-2012
Publisher: Elsevier
Journal Title: Progress in Neuro-Psychopharmacology and Biological Psychiatry
Volume: 38
Issue: 2
Start Page: 183
End Page: 189
Publisher DOI: 10.1016/j.pnpbp.2012.03.006
PMID: 22484386
Abstract: Adult neurogenesis in dentate gyrus (DG) is involved in the action mechanism of mood stabilizers. However, it is poorly understood how mood stabilizers affect adult neurogenesis in DG. Neurogenesis consists of proliferation, survival (anti-apoptosis) and differentiation of neural precursor cells in adult DG. Using in vitro culture of adult rat DG-derived neural precursor cells (ADP), we have already shown that four mood stabilizers, such as lithium (Li), valproate (VPA), carbamazepine (CBZ) and lamotrigine (LTG), commonly decrease staurosporine (STS)-induced apoptosis of ADP. These suggest that the common anti-apoptotic effect of mood stabilizers could be involved in mood-stabilizing effects. Past studies have shown that Li and VPA increase the expression of Bcl-2, an anti-apoptotic gene. In addition, it has been shown that Li decreases the expression of p53, which plays a prominent role in apoptosis and regulates the expression of Bcl-2. Therefore, p53 and Bcl-2 can be considered to mediate the common anti-apoptotic effects of Li, VPA, CBZ and LTG. To elucidate the molecular mechanism underlying the common anti-apoptotic effects of mood stabilizers, we investigated the effects of Li, VPA, CBZ and LTG on STS-induced expression changes of p53, Bcl-2 and other p53-related molecules using SH-SY5Y cells as a model of neural precursor-like cells. STS increased the expression of p53 and decreased that of Bcl-2. These effects of STS on p53 and Bcl-2 are restored by all of Li, VPA, CBZ and LTG. In addition, p53 overexpression decreased the expression of Bcl-2. Taken together, these results suggest that p53 and Bcl-2 may be involved in a part of mood-stabilizing effects.
Type: article (author version)
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 朴 秀賢

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