巴金森氏症 (Parkinson’s disease) 是一種普遍的神經退化性疾病，其特徵在於黑質多巴胺能神經元選擇性的喪失，並導致身體震顫、僵直、運動遲緩等現象。雖然巴金森氏症的病因目前還是未知的，但可透過產生與巴金森氏症相似症狀的多巴胺衍生物 6-羥多巴胺 (6-hydroxydopamine, 6-OHDA) 來深入了解疾病的過程。6-羥多巴胺已被證實可引起細胞壓力相關基因的轉錄變化及內質網未摺疊蛋白反應。因此本研究欲探討具有抗氧化、抗發炎活性的木犀草素 (luteolin) 是否具有保護 PC12 類神經細胞免於 6-羥多巴胺所誘導的內質網壓力及氧化傷害的功效。研究結果發現，6-羥多巴胺可造成細胞死亡，且其毒性與劑量及時間呈正相關。6-羥多巴胺能誘導細胞內活性氧 (ROS) 的生成也導致細胞停滯於 S 期。6-羥多巴胺能活化 PERK-eIF2α-ATF4 這條典型的未摺疊蛋白質反應 (UPR) 並誘導下游的伴隨蛋白 GRP78 和轉錄因子 CHOP 的表現。6-羥多巴胺能誘導 PC12 細胞中 Bcl-2 家族基因及促凋亡、壓力感測及細胞週期相關之基因表現。添加木犀草素可降低 6-羥多巴胺的細胞毒性、清除活性氧，並減少停滯於 S 期的細胞。木犀草素也能抑制 UPR 訊息路徑及下游轉錄因子的活化，降低細胞中促凋亡、誘發壓力感測基因及細胞週期調控相關的基因表現。 Parkinson’s disease (PD) is a common neurodegenerative diseasecharacterized by the selective loss of dopaminergic neurons in the substantianigra, resulting in tremor, rigidity, and bradykinesia. Although the etiology isunknown, insight into the disease process comes from the dopamine (DA)derivative, 6-hydroxydopamine (6-OHDA), which produces PD-like symptoms.The neurotoxin 6-OHDA has been shown to cause transcriptional changesassociated with cellular stress and the endoplasmic reticulum unfolded proteinresponse. The aim of this study is to study whether luteolin can protect PC12cells from 6-OHDA-induced endoplasmic reticulum stress and oxidative stress.In this research, it was found that 6-OHDA causes PC12 cell death doseandtime-dependently. 6-OHDA induced intracellular generation of reactiveoxygen species, and cell cycle arrest at S phase. One canonical arm of the UPR,PERK-eIF2-ATF4 splicing, and ER chaperone GRP78 and CHOP wereactivated after treatment with 6-OHDA. 6-OHDA also induced Bcl-2 family,stress sensor and cell cycle regulatory gene expression in PC12 cells.Addition of luteolin restored the cell viability, reduced ROS level and cellcycle arrest. Luteolin attenuated expression of genes involved in cell cycleregulation, unfolded protein response (UPR) and apoptosis.
