鋰鹽對 C6 神經膠瘤細胞粒線體生合成的作用
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- coact ivator-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 P GC-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。
Effects of Lithium treatment on mitochondrial biogenesis in C6 glioma cells
Lithium has been used to treat manic depression, and has been shown to ex ert cytoprotective effect in vivo and in vitro. Previously, we have found tha t lithium increases ATP production in C6 glioma cells, suggesting lithium may stimulate mitochondria biogenesis in C6 glioma cells. In the present st udy, we investigate the effect of lithium treatment on mitochondria biogen esis in C6 glioma cells. Incubation of cells with lithium increased mitochon drial mass and DNA copy number, as demonstrated by RT-PCR of mitoch ondrial DNA-specific ND-1 region 、 mtTFA(mitochondrial transcriptiona l factor A) and PCR of ND-1 control region, respectively. Lithium treatme nt was also found to increase the ATP production, ROS generation, and res piration rate. Recently PGC-1has been shown to play a central role in m itochondria biogenesis. We next examined whether lithium induces PGC-1
protein expression. Indeed, lithium induces PGC-1 expression in a ti
me-response and dose-dependent manners. PGC-1induction by lithium i n mediation through reactive oxygen species (ROS) 。 UCP-2 expression a nd mitochondria biogenesis exerts through PGC-1 modulation.