The secretory phenotype of senescent astrocytes isolated from Wistar newborn rats changes with anti-inflammatory drugs, but does not have a short-term effect on neuronal mitochondrial potential
The secretory phenotype of senescent astrocytes isolated from Wistar newborn rats changes with anti-inflammatory drugs, but does not have a short-term effect on neuronal mitochondrial potential
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DOI：
10.1007/s10522-018-9767-3
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发表时间：
2018-10-01
期刊：
影响因子：
4.5
通讯作者：
Konigsberg, Mina
中科院分区：
文献类型：
--
作者：
Angel Maciel-Baron, Luis;Lizbeth Morales-Rosales, Sandra;Konigsberg, Mina
在中枢神经系统（CNS）中，衰老的星形胶质细胞与神经退行性变有关。衰老细胞分泌促炎因子的复杂混合物，其统称为衰老相关分泌表型（SASP）。SASP组分可以根据细胞类型、衰老诱导剂和时间而变化。SASP主要在成纤维细胞和上皮细胞中进行研究，但在CNS中知之甚少。在这里，SASP的配置文件中分离的衰老星形胶质细胞诱导衰老的氧化应激或蛋白酶体抑制Wistar新生大鼠进行了分析。衰老星形胶质细胞主要分泌趋化因子和IL-1 α，但不分泌IL-6。评价了抗炎药萝卜硫素（SFN）和脱氢表雄酮（DHEA）对SASP谱的影响。我们的研究结果表明，SFN和DHEA减少IL-1 α分泌，同时增加IL-10，从而将SASP修改为较少的抗炎特性。将原代神经元置于从药物处理的衰老星形胶质细胞获得的条件培养基中，并评估其线粒体膜电位。
In the central nervous system (CNS), senescent astrocytes have been associated with neurodegeneration. Senescent cells secrete a complex mixture of pro-inflammatory factors, which are collectively called Senescence Associated Secretory Phenotype (SASP). The SASP components can vary depending on the cell type, senescence inducer and time. The SASP has been mainly studied in fibroblasts and epithelial cells, but little is known in the context of the CNS. Here, the SASP profile in senescent astrocytes isolated from Wistar newborn rats induced to senescence by oxidative stress or by proteasome inhibition was analyzed. Senescent astrocytes secreted predominantly chemokines and IL-1 alpha, but no IL-6. The effect of the anti-inflammatory drugs, sulforaphane (SFN) and dehydroepiandrosterone (DHEA), on the SASP profile was evaluated. Our results showed that SFN and DHEA decreased IL-1 alpha secretion while increasing IL-10, thus modifying the SASP to a less anti-inflammatory profile. Primary neurons were subjected to the conditioned media obtained from drug-treated senescent astrocytes, and their mitochondrial membrane potential was evaluated.