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Secretogranin III may be an indicator of paraquat-induced astrocyte activation and affects the recruitment of BDNF during this process.

Int. J. Mol. Med.2018 Dec;42(6):3622-3630. doi:10.3892/ijmm.2018.3909. Epub 2018 Oct 01
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摘要


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.

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