探討薯蕷皂素調控ERK磷酸化對PC12細胞株早期分化之作用

Diosgenin稱為薯蓣皂甘素，萃取於植物山藥的根，是類固醇皂元的一種。文獻指出，diosgenin能夠抑制發炎反應、降血糖、抗氧化等效應。由於diosgenin的結構與雌激素相似，但是否能夠誘導神經細胞分化這方面並不清楚。本篇研究將老鼠腎上腺髓質的嗜鉻細胞瘤分別以不同濃度的diosgenin刺激，結果顯示當細胞受到20μM diogenin刺激下到達第七天時，會具有類神經纖維生長 (neurite outgrowth)之分化、並表現神經細胞特有蛋白Tuj1，更進一步得知，diosgenin會誘導Erk1/2磷酸化的增加，並且會減少Akt的活性。若加入Mek1/2的抑制劑U0126，會阻斷Erk1/2的磷酸化及抑制diosgenin誘導PC12細胞分化的能力。由於PC12細胞株並沒有ERα、ERβ，因此也證實diosgenin非依賴於ER調控。綜合以上結果證明diosgenin不需要透過ER並且能活化MAPK / ERK pathway達到誘導PC12細胞分化的現象。

關鍵字

薯蕷皂素；早期分化

並列摘要

Diosgenin, a steroidal sapogenin is extracted from the root of wild yam (dioscorea villosa). Diosgenin has numerous biological activities. It can reduce higher sugar concentration in blood serum, inhibit over-inflammatory response as well as play an antioxidant against reactive oxygen species in cells under oxidative stresses. Recently, it has been reported that re-differentiation of osteosacroma cells was affected by diosgenin. However, the influence of diosgenin on neuron cell differentiation remains unknown. To this purpose, the present study aimed at understanding the physiological role of diosgenin in association with neurite development. Our results showed that under treatment of diosgenin 20 μM for 7days, it can induce PC12 cell differentiation, manifesting by the outgrowth of neurite and detection of the increased expression of the Tuj1 protein. In the meantime, Raf, Mek and Erk1/2 were appeared to be phosphorylated. Contrastily, the reduced expression of PKB/Akt was examined in PC12 cells treated with diosgenin. Moreover, outgrowth of neurite in diosgenin-treated PC12 cells was inhibited by treatment of the MEK inhibitor U0126. These data presented reveal that the potential mechanism of diosgenin on PC12 cells differentiation is involved in activation of the ERK pathway. In addition, we demonstrated neurite differentiation whose PC12 cell line lacking estrogen receptor also exhibited increasing expression of Erk1/2. Taken together, we concluded that cell differentiation of neurite in PC12 cells in response to diosgenin is dependent upon Erk activation, which is of ER-independence.

並列關鍵字

PC12 cells ； diosgenin

參考文獻

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探討薯蕷皂素調控ERK磷酸化對PC12細胞株早期分化之作用

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