Activation of tumor suppressor protein PTEN and induction of apoptosis are involved in cAMP-mediated inhibition of cell number in B92 glial cells

NEUROSCIENCE LETTERS

卷:497

Article

Sugimoto, Naotoshi¹  Miwa, Shinji²  Ohno-Shosaku, Takako³  Tsuchiya, Hiroyuki²  Hitomi, Yoshiaki⁴  Nakamura, Hiroyuki⁴  Tomita, Katsuro²  Yachie, Akihiro⁵  Koizumi, Shoichi⁶ 

[1] Kanazawa Univ, Grad Sch Med Sci, Dept Physiol, Kanazawa, Ishikawa 9208640, Japan

[2] Kanazawa Univ, Grad Sch Med Sci, Dept Orthoped Surg, Kanazawa, Ishikawa 9208640, Japan

[3] Kanazawa Univ, Grad Sch Med Sci, Dept Impairment Study, Kanazawa, Ishikawa 9208640, Japan

[4] Kanazawa Univ, Grad Sch Med Sci, Dept Publ Hlth, Kanazawa, Ishikawa 9208640, Japan

[5] Kanazawa Univ, Grad Sch Med Sci, Dept Pediat, Kanazawa, Ishikawa 9208640, Japan

[6] Kanazawa Univ, United Grad Sch Child Dev, Kanazawa, Ishikawa 9208640, Japan

关键词: cAMP;    Akt;    PTEN;    Cell number;    Apoptosis;    VASP;   

DOI  :  10.1016/j.neulet.2011.04.028

来源: Elsevier

【 摘 要 】

During brain development, cAMP induces morphological changes and inhibits growth effects in several cell types. However, the molecular mechanisms underlying the growth inhibition remain unknown. Tumor suppressor protein phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a lipid phosphatase that inhibits the phosphoinositide 3-kinase (PI3K) pathway. The phosphorylation of Akt, which is one of the key molecules downstream of PI3K, inhibits apoptosis. In this study, we investigated the role of PTEN in cAMP-mediated growth inhibition. 892 rat glial cells were treated with 2 different cAMP stimulatory agents, a phosphodiesterase (PDE) inhibitor and a beta-adrenoceptor agonist. Both cAMP stimulatory agents induced marked morphological changes in the cells, decreased cell number, decreased Akt phosphorylation, activated PTEN, cleaved caspase-3, and induced the condensation and fragmentation of nuclei. These results indicate that the cAMP stimulatory agents induced apoptosis. Protein phosphatase inhibitor prevented cAMP-induced dephosphorylation of PTEN and Akt. In addition, cAMP analogs and Epac-selective agonists affected PTEN and Akt activities. These results suggested that cAMP-induced apoptosis may be mediated by PTEN activation and Akt inhibition through protein phosphatase in B92 cells. Our results provide new insight into the role of PTEN in cAMP-induced apoptosis in glial cells. (C) 2011 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

Free