Oxidative Stress-Induced Attenuation of Thrombospondin-1 Expression in Primary Rat Astrocytes
Oxidative Stress-Induced Attenuation of Thrombospondin-1 Expression in Primary Rat Astrocytes
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DOI：
10.1002/jcb.22732
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发表时间：
2011-01-01
影响因子：
4
通讯作者：
Tzeng, Shun-Fen
中科院分区：
文献类型：
--
作者：
Chen, Jen-Kun;Zhan, Yan-Jie;Tzeng, Shun-Fen
星形胶质细胞是中枢神经系统 (CNS) 中的主要神经胶质细胞群，可以分泌血小板反应蛋白 (TSP)-1，在 CNS 发育和组织修复过程中的突触发生和轴突萌芽中发挥作用。然而，对于氧化应激条件下星形胶质细胞TSP-1表达的调控知之甚少。在这里，使用一种低氧模拟试剂氯化钴（CoCl2）来启动原代大鼠星形胶质细胞中缺氧诱导的氧化应激。发现浓度范围为 0.1-0.5 mM 的 CoCl2 不会导致原代大鼠星形胶质细胞明显的细胞死亡。然而，0.2-0.5 mM 的 CoCl2 会增加细胞内活性氧 (ROS) 水平和甘油醛 3-磷酸脱氢酶 (GAPDH) 基因表达，这被认为是氧化损伤的标志。我们进一步发现星形胶质细胞中 TSP-1 mRNA 的表达受到 CoCl2 的剂量和时间依赖性抑制。与仅暴露于 CoCl2 的培养物中检测到的水平相比，在丝裂原激活蛋白激酶/细胞外信号调节激酶 (MAPK/ERK) 抑制剂（U0126 和 PD98059）存在下，暴露于 CoCl2 的星形胶质细胞中的 TSP-1 mRNA 水平有所增加。此外，添加有效的抗氧化剂 N-乙酰半胱氨酸 (NAC) 可以阻断 CoCl2 对 TSP-1 mRNA 表达的抑制。因此，我们得出结论，CoCl2 通过可能涉及 MAPK/ERK 的 ROS 机制抑制星形胶质细胞中的 TSP-1 mRNA 表达。这种抑制可能发生在中枢神经系统损伤后，并损害星形胶质细胞对受损中枢神经系统组织中神经突生长的支持功能。 J.细胞。生物化学。 112: 59-70, 2011。(C) 2010 Wiley-Liss, Inc.
Astrocytes, the major glial population in the central nervous system (CNS), can secrete thrombospondin (TSP)-1 that plays the role in synaptogenesis and axonal sprouting during CNS development and tissue repair. However, little is known about the regulation of TSP-1 expression in astrocytes under oxidative stress condition. Here, a hypoxic mimetic reagent, cobalt chloride (CoCl2), was used to initiate hypoxia-induced oxidative stress in primary rat astrocytes. CoCl2 at the concentration range of 0.1-0.5 mM was found to cause no significant cell death in primary rat astrocytes. However, CoCl2 at 0.2-0.5 mM increased intracellular reactive oxygen species (ROS) levels and glyceraldehyde 3-phosphate dehydrogenase (GAPDH) gene expression that is known as a hallmark for oxidative damage. We further found that TSP-1 mRNA expression in astrocytes was inhibited dose- and time-dependently by CoCl2. TSP-1 mRNA levels were increased in CoCl2-exposed astrocytes in the presence of the inhibitors (U0126 and PD98059) of mitogen-activated protein kinase/extracellular signal-regulated kinases (MAPK/ERK), when compared to that detected in the culture only exposed to CoCl2. Moreover, the inhibition in TSP-1 mRNA expression by CoCl2 was blocked by the addition of the potent antioxidant, N-acetylcysteine (NAC). Thus, we conclude that CoCl2 inhibits TSP-1 mRNA expression in astrocytes via a ROS mechanism possibly involving MAPK/ERK. This inhibition may occur after CNS injury and impair the supportive function of astrocytes on neurite growth in the injured CNS tissues. J. Cell. Biochem. 112: 59-70, 2011. (C) 2010 Wiley-Liss, Inc.