鋰鹽對 C6 神經膠瘤細胞粒線體生合成的作用 Effects of Lithium treatment on mitochondrial biogenesis in C6 glioma cells

鋰鹽對 C6 神經膠瘤細胞粒線體生合成的作用

Effects of Lithium treatment on mitochondrial biogenesis in C6

glioma cells

中文摘要

鋰鹽 ( Lithium Chloride, LiCl ) 是長期用於治療憂鬱症及躁鬱症的藥物。近來的

研究發現鋰鹽在細胞內或細胞外的實驗中具有細胞保護作用。我們發現在C6 神

經膠瘤細胞中用鋰鹽刺激可增加ATP 的產生，所以我們猜測鋰鹽在 C6 神經膠瘤

細胞中可能刺激粒線體的生合成作用(Biogenesis)。本研究利用 C6 神經膠瘤細胞

探討鋰鹽刺激對粒線體生合成作用的影響。本研究發現利用鋰鹽刺激C6 神經膠

瘤細胞推測可以增加粒線體的量。鋰鹽也可以增加細胞的ATP 的產生、reactive

oxygen species (ROS)、呼吸速率，並可以增加粒線體去氧核醣核?酸複拷貝數 (DNA copy number )。而利用 RT-PCR 來看 ND-1 與 mtTFA(mitochondrial

transcriptional factor A)之 mRNA 表現以及利用 PCR 粒線體基因 ND-1 region 來觀 察粒線體生合成。近來發現 PPAR-　 coactivator-1 　 (PGC-1 　在粒線體生合 成扮演重要的中心角色，所以我們想要研究當鋰鹽刺激細胞時PGC-1 　是否有 表現。在利用鋰鹽刺激細胞，我們確實可以看到在不同時間點以及不同劑量鋰鹽 添加會促使PGC-1 　表現會上升。而推測 PGC-1 　蛋白表現可能是經過 ROS 而 來的，PGC-1 　會誘發 UCP-2 表現以及粒線體生合成作用。 英文摘要

Lithium has been used to treat manic depression, and has been shown to exert cytoprotective effect in vivo and in vitro. Previously, we have found that lithium increases ATP production in C6 glioma cells, suggesting lithium may stimulate mitochondria biogenesis in C6 glioma cells. In the present study, we investigate the effect of lithium treatment on mitochondria biogenesis in C6 glioma cells. Incubation of cells with lithium increased mitochondrial mass and DNA copy number, as

demonstrated by RT-PCR of mitochondrial DNA-specific ND-1 region、

mtTFA(mitochondrial transcriptional factor A) and PCR of ND-1 control region, respectively. Lithium treatment was also found to increase the ATP production, ROS generation, and respiration rate. Recently PGC-1 　　has been shown to play a central role in mitochondria biogenesis. We next examined whether lithium induces PGC-1 　　 protein expression. Indeed, lithium induces PGC-1 　　 expression in a time-response and dose-dependent manners. PGC-1 　　 induction by lithium in mediation through reactive oxygen species (ROS)。UCP-2 expression and mitochondria biogenesis exerts through PGC-1 　 modulation.