Activation of tumor suppressor protein PTEN and induction of apoptosis are involved in cAMP-mediated inhibition of cell number in B92 glial cells
Activation of tumor suppressor protein PTEN and induction of apoptosis are involved in cAMP-mediated inhibition of cell number in B92 glial cells
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DOI：
10.1016/j.neulet.2011.04.028
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发表时间：
2011-06-15
影响因子：
2.5
通讯作者：
Koizumi, Shoichi
中科院分区：
文献类型：
--
作者：
Sugimoto, Naotoshi;Miwa, Shinji;Koizumi, Shoichi
在大脑发育过程中，cAMP诱导形态学变化并抑制几种细胞类型的生长效应。然而，生长抑制的分子机制仍然未知。10号染色体上缺失的肿瘤抑制蛋白磷酸酶和张力蛋白同源物（PTEN）是抑制磷酸肌醇3-激酶（PI 3 K）途径的脂质磷酸酶。Akt是PI 3 K下游的关键分子之一，其磷酸化抑制细胞凋亡。在这项研究中，我们研究了PTEN在cAMP介导的生长抑制中的作用。用2种不同的cAMP刺激剂，磷酸二酯酶（PDE）抑制剂和β-肾上腺素受体激动剂处理892个大鼠胶质细胞。两种cAMP刺激剂均诱导细胞发生显著的形态学变化，细胞数量减少，Akt磷酸化减少，PTEN活化，caspase-3裂解，并诱导细胞核浓缩和碎裂。这些结果表明cAMP刺激剂诱导细胞凋亡。蛋白磷酸酶抑制剂阻止cAMP诱导的PTEN和Akt的去磷酸化。此外，cAMP类似物和Epac选择性激动剂影响PTEN和Akt活性。这些结果提示cAMP诱导的B 92细胞凋亡可能是通过蛋白磷酸酶介导的PTEN激活和Akt抑制而实现的。我们的研究结果提供了新的见解，在cAMP诱导的神经胶质细胞凋亡的PTEN的作用。(C)2011爱思唯尔爱尔兰有限公司保留所有权利。
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.