Protection of ischemic brain cells is dependent on astrocyte-derived growth factors and their receptors
Protection of ischemic brain cells is dependent on astrocyte-derived growth factors and their receptors
复制标题
DOI：
10.1016/j.expneurol.2006.04.014
复制
发表时间：
2006-09-01
影响因子：
5.3
通讯作者：
Hsueh, Chi-Mei
中科院分区：
文献类型：
--
作者：
Lin, Chi-Hsin;Cheng, Fu-Chou;Hsueh, Chi-Mei
一种体外缺血模型（缺氧、缺糖及无血清）被用于研究可能导致脑缺血的细胞和分子机制。我们先前已经证明，源自缺血小胶质细胞的上清液可通过释放胶质细胞源性神经营养因子（GDNF）和转化生长因子 -β1来保护缺血脑细胞。在本研究中，我们探讨缺血星形胶质细胞的产物是否也能以类似方式保护缺血小胶质细胞、星形胶质细胞和神经元。在不同缺血时间后收集缺血星形胶质细胞的上清液，并在体外缺血条件下分别与小胶质细胞、星形胶质细胞或神经元一起培养。然后通过蛋白质印迹法、酶联免疫吸附测定（ELISA）、台盼蓝拒染法和免疫阻断试验来确定星形胶质细胞源性上清液保护作用的相关成分。结果显示，在体外缺血条件下，加入星形胶质细胞源性上清液可显著增加存活的小胶质细胞、星形胶质细胞和神经元的数量。星形胶质细胞上清液对缺血小胶质细胞的保护作用依赖于转化生长因子 -β1和神经营养因子 -3（NT - 3），缺血星形胶质细胞受GDNF保护，缺血神经元受NT - 3保护。此外，体外缺血可使小胶质细胞中转化生长因子 -β1和NT - 3受体、星形胶质细胞中GDNF受体以及神经元中NT - 3受体的蛋白表达增加。这些结果表明，星形胶质细胞对缺血脑细胞的保护不仅依赖于缺血星形胶质细胞释放的因子，还依赖于反应细胞上存在的受体类型。进一步提示了转化生长因子 -β1、GDNF和NT - 3在脑缺血控制中的治疗潜力。（c）2006年由爱思唯尔公司出版
An in vitro ischemia model (oxygen, glucose, and serum deprivation) is used to investigate the possible cellular and molecular mechanisms responsible for cerabral ischemia. We have previously demonstrated that supernatants derived from ischemic microglia can protect ischemic brain cells by releasing GDNF and TGF-beta 1. In the present study, we investigate whether products of ischemic astrocytes can also protect ischemic microglia, astrocytes, and neurons in a similar manner. Supernatants from ischemic astrocytes were collected after various periods of ischemia and incubated with microglia, astrocytes, or neurons individually, under in vitro ischemic conditions. The components responsible for the protective effects of astrocyte-derived supernatants were then identified by Western blot, ELISA, trypan blue dye exclusion, and immunoblocking assays. Results showed that under conditions of in vitro ischemia the number of surviving microglia, astrocytes, and neurons was significantly increased by the incorporation of the astrocyte-derived supernatants. Astrocyte supernatant-mediated protection of ischemic microglia was dependent on TGF-beta 1 and NT-3, ischemic astrocytes were protected by GDNF, and ischemic neurons were protected by NT-3. In addition, protein expression of TGF-beta 1 and NT-3 receptors in microglia, GDNF receptors in astrocytes, and NT-3 receptors in neurons was increased by in vitro ischemia. These results suggest that astrocyte-derived protection of ischemic brain cells is dependent not only on factors released from the ischemic astrocytes, but also on the type of receptor present on the responding cells. Therapeutic potential of TGF-beta 1, GDNF, and NT-3 in the control of cerebral ischemia is further suggested. (c) 2006 Published by Elsevier Inc.