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首页> 外文期刊>The European Journal of Neuroscience >Mechanical lesion activates newly identified NFATc1 in primary astrocytes: implication of ATP and purinergic receptors.
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Mechanical lesion activates newly identified NFATc1 in primary astrocytes: implication of ATP and purinergic receptors.

机译：机械损伤激活原发星形胶质细胞中新发现的NFATc1：暗示ATP和嘌呤能受体。

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摘要

Ca2+-dependent calcineurin is upregulated in reactive astrocytes in neuroinflammatory models. Therefore, the fact that the nuclear factor of activated T cells (NFAT) is activated in response to calcineurin qualifies this family of transcription factors with immune functions as candidates to mediate astrogliosis. Brain trauma induces a neuroinflammatory state in which ATP is released from astrocytes, stimulating calcium signalling. Our goal here is to characterize NFATc1 and NFATc2 in mouse primary astrocyte cultures, also exploring the implication of NFAT in astrocyte activation by mechanical lesion. Quantitative reverse transcriptase-polymerase chain reaction, Western blot analysis and immunofluorescence microscopy identified NFATc1 in astrocytes, but not NFATc2. Moreover, NFATc1 was expressed in the cytosol of resting astrocytes, whereas activation of the Ca2+-calcineurin pathway by ionomycin translocated NFATc1 to the nucleus, which is a requirement for activation. The implication of astrocytic NFATin brain trauma was analysed using an in vitro scratch lesion model. Mechanical lesion caused a rapid NFATc1 translocation that progressed throughout the culture as a gradient and was maintained for at least 4 h. We also demonstrate that ATP, released by lesion, is a potent inducer of NFATc1 translocation and activation. Moreover, the use of P2Y receptor modulators showed that such ATP action is mediated by stimulation of several G(q)-protein-coupled P2Y purinergic receptors, among which P2Y(1) and P2Y(6) are included. In conclusion, this work provides evidence that newly identified NFATc1 is translocated in astrocytes in response to lesion following a pathway that involves ATP release and activation of metabotropic purinergic receptors.
机译：在神经炎性模型中，Ca2 +依赖性钙调神经磷酸酶在反应性星形胶质细胞中上调。因此，激活的T细胞核因子（NFAT）响应钙调神经磷酸酶而被激活这一事实使具有免疫功能的转录因子家族成为介导星形胶质瘤的候选者。脑外伤可诱发神经炎症状态，其中星形胶质细胞释放ATP，刺激钙信号传导。我们的目标是表征小鼠原代星形胶质细胞培养物中的NFATc1和NFATc2，还探讨了NFAT在机械损伤引起的星形胶质细胞激活中的意义。定量逆转录聚合酶链反应，Western印迹分析和免疫荧光显微镜鉴定出星形胶质细胞中的NFATc1，但不是NFATc2。此外，NFATc1在静止的星形胶质细胞的细胞质中表达，而离子霉素对Ca2 +-钙调神经磷酸酶途径的激活将NFATc1转移到细胞核，这是激活的必要条件。使用体外划痕病变模型分析了星形细胞NFATin对脑部创伤的影响。机械损伤导致NFATc1快速移位，在整个培养过程中均呈梯度，并持续至少4 h。我们还证明了由病变释放的ATP是NFATc1易位和激活的有效诱导剂。此外，使用P2Y受体调节剂表明，这种ATP的作用是通过刺激几个G（q）-蛋白偶联的P2Y嘌呤能受体介导的，其中包括P2Y（1）和P2Y（6）。总之，这项工作提供了证据，表明新发现的NFATc1通过涉及ATP释放和代谢型嘌呤能受体活化的途径响应病变而在星形胶质细胞中易位。

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