Department of Forensic Genetics and Biology, School of Forensic Medicine, China Medical University, Shenyang, Liaoning 110122, P.R. China.
Department of Forensic Medicine, Baotou Medical College, Baotou, Inner Mongolia 014040, P.R. China.
Int J Mol Med. 2018 Dec;42(6):3622-3630. doi: 10.3892/ijmm.2018.3909. Epub 2018 Oct 1.
Astrocyte activation has been described as a multi‑stage defensive response, which is characterized by the morphological alteration of astrocytes and the overexpression of intermediate filament proteins. However, the functional mechanism of the secretion system in activated astroglia remains unclear. It has previously been demonstrated that secretogranin II, a member of the granin family, may be involved in the sorting and expression of inflammatory factors and excitatory neurotransmitters in paraquat (PQ)‑induced astroglial activation. Secretogranin III (SCG3) has been reported to represent an important component of the regulated secretory pathway in neuroendocrine cells; however, its role as an anchor protein of dense‑core vesicles in astrocytes remains to be elucidated. In the present study, a PQ‑activated U118MG astrocytoma cell model established in our previous study was used to investigate the effects of SCG3. The results revealed that SCG3 was highly expressed and subsequently released from cells in response to PQ. Inhibition of SCG3 expression via transfection with small interfering RNA partially restored astrocyte morphology, but did not affect the expression of astrocytic factors. Further studies investigating the association between SCG3 and other cellular factors were conducted, in order to determine the expression levels and subcellular localization of these proteins. Neurotrophins and inflammatory factors exhibited an increase in characteristic expression patterns, paralleling the alterations in SCG3 expression. The results further demonstrated that brain‑derived neurotrophic factor partially colocalized with SCG3‑positive vesicles; however, the localization of interleukin‑6 was not affected. In conclusion, SCG3 may be involved in PQ‑induced astrocyte activation via regulation of the expression and selective recruitment of cellular factors, thus suggesting that SCG3 may represent an indicator of astrocyte activation.
星形胶质细胞的激活被描述为一个多阶段的防御反应，其特征是星形胶质细胞的形态改变和中间丝蛋白的过度表达。然而，激活的星形胶质细胞分泌系统的功能机制尚不清楚。先前已经证明，神经颗粒素 II，颗粒素家族的一员，可能参与百草枯（PQ）诱导的星形胶质细胞激活中炎症因子和兴奋性神经递质的分拣和表达。已经报道神经颗粒素 III（SCG3）是神经内分泌细胞中受调控分泌途径的重要组成部分；然而，其作为星形胶质细胞致密核心囊泡的锚蛋白的作用仍有待阐明。在本研究中，使用我们之前研究中建立的 PQ 激活的 U118MG 星形细胞瘤细胞模型来研究 SCG3 的作用。结果表明，SCG3 在受到 PQ 刺激后高度表达并随后从细胞中释放。通过小干扰 RNA 转染抑制 SCG3 表达部分恢复了星形胶质细胞的形态，但不影响星形胶质细胞因子的表达。进一步研究了 SCG3 与其他细胞因子之间的关联，以确定这些蛋白质的表达水平和亚细胞定位。神经生长因子和炎症因子表现出特征性表达模式的增加，与 SCG3 表达的改变平行。结果进一步表明，脑源性神经营养因子部分与 SCG3 阳性囊泡共定位；然而，白细胞介素-6 的定位不受影响。总之，SCG3 可能通过调节细胞因子的表达和选择性募集参与 PQ 诱导的星形胶质细胞激活，因此 SCG3 可能代表星形胶质细胞激活的指标。
