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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
| 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 | | Hippocampus | | Dentate gyrus | | Adult neurogenesis | | Bcl-2 |
| 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) |
| URI: | http://hdl.handle.net/2115/50363 |
| 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)
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Submitter: 朴 秀賢
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