葡萄糖調控蛋白78 (Glucose-Regulated Protein 78, GRP78) 位於內質網中，具有鈣離子結合能力以及保護子的功能，能夠幫助新合成之蛋白質的折疊，使其具有正確的功能和結構。當細胞處於逆境環境下，會誘發細胞中GRP78表現增加。根據之前的研究發現，在鈣離子攜帶劑A23187和內質網上的鈣離子通道抑制劑thapsigargin (TG) 的個別處理下，皆會造成細胞質的鈣離子濃度上升，而引發GRP78的合成增加。這和90kDa熱休克蛋白抑制劑geldanamycin (GA) 所造成的細胞內質網中蛋白質的摺疊不正常，而誘導GRP78合成增加的機制是不相同的。此外，細胞在此三種藥物處理下，GRP78在細胞中的超微分布也尚未明瞭。
我們以9L大白鼠腦腫瘤細胞為材料，探討A23187、TG和GA誘發GRP78表現所產生的GRP78的超微分布。利用共軛焦顯微鏡技術，我們發現在A23187，TG和GA的個別處理下，GRP78會重新分布，不再完全位於內質網中﹔但GA所誘發GRP78的重新分布則較無此明顯趨勢。另一方面，藉由胞器分離實驗、共軛焦顯微鏡技術和免疫膠體金顯微鏡技術的相互證明，我們首次發現，細胞在A23187、TG和GA處理下，所誘發的GRP78的確會出現於粒線體之中。因此，我們可以歸納出，相對於GA而言，A23187和TG所誘發GRP78表現的機制應是較一致的。除此之外，在藥物處理過後，GRP78也不只僅存在於內質網之中，會轉而出現於粒線體，而存在於粒線體之中的GRP78也必定扮演著重要且未知的角色。

In the previous study, it has been found that the syntheses of the 78kDa glucose-regulated protein (GRP78) were vigorously induced by stresses, such as A23187, thapsigargin (TG) and geldanamycin (GA) in 9L rat brain tumor (RBT) cell line. In this study, we have found that an 8h treatment with either 2 μM A23187 or 300 nM TG caused the redistribution of GRP78 in 9L RBT cells. GRP78 exhibited the pattern outside the ER when respectively treated with A23187 and TG, but this phenomenon was less obvious after 5 μM GA treatment for 8h. Although GRP78 are primarily localized in the endoplasmic reticulum (ER), subcellular fractionation study showed that the stress-induced GRP78 was in the mitochondria-enriched fraction in from 9L RBT cells. Furthermore, confocal microscopic and immunogold electron microscopic studies confirmed that the stress-induced GRP78 was indeed localized in mitochondria. These results indicate that GRP78 is not present exclusively in the ER after stressed. This is the first report demonstrating that GRP78 is localized in mitochondria in 9L RBT cells after being exposed to GRP78-inducing stresses.

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