臺灣博碩士論文加值系統

炭疽病(Anthrax)是一種由炭疽桿菌(Bacillus anthracis)感染所引起的疾病，通常造成組織缺氧壞死、貧血等症狀，嚴重時導致死亡；引起高死亡率的機制仍不清楚。炭疽致死毒素(lethal toxin，LT)是炭疽桿菌的主要毒力因子，由保護性抗原 (protective antigen，簡稱為PA）與致死因子（lethal factor，簡稱為LF）二種蛋白組合而成。PA會結合到目標細胞表面的炭疽毒素接受器（anthrax toxin receptor），而和LT結合後，可使LF 進到細胞質。LF是一需要和鋅離子結合才能作用的蛋白酵素 （zinc-dependent metalloprotease），會切割MAPKK(mitogen-activated protein kinase kinase，MEK)的N端，因此破壞MAPK(mitogen-activated protein kinase)訊息傳導路徑：包括ERK (extracellular signal-regulated kinase)，p38和JNK (c-Jun N-terminal kinase)。在炭疽病所造成的死亡會有貧血與組織缺氧壞死，因此我們進一步分析是否LT能抑制紅血球分化。我們發現在K562 細胞前處理LT能抑制GTP (guanosine 5'-triphosphate) 所誘導之紅血球分化。在此研究，利用西方墨點法（Western blotting）來偵測LT之所以能抑制紅血球分化與哪個訊息傳遞路徑有關。本實驗中發現，LT之所以能抑制紅血球分化是透過抑制p38訊息傳導路徑。

Anthrax, a disease caused by Bacillus anthracis infection, usually coincides with hypoxic tissue damages, anemia and lethality and the mechanism associated with its high mortality is not yet clear. Anthrax lethal toxin (LT) is the major virulence factor produced by Bacillus anthracis, which that composed of two proteins: protective antigen (PA) and lethal factor (LF). PA binds to toxin receptors on the surfaces of target cells and allows entry of LF into the cytosol. LF is a zinc-dependent metalloprotease that cleaves the N-terminus of mitogen-activated protein kinase kinase (MKKs/MEKs), and thus disrupts the mitogen-activated protein kinase (MAPK) pathways: the ERK (extracellular signal-regulated kinase), p38 and JNK (c-Jun N-terminal kinase). Since anemia and hypoxic tissue damages are involved in anthrax-mediated mortality, these observations prompt us to analyze whether LT could block erythroid differentiation. Based on our data, we found that LT pretreatments could block GTP induced erythrocytic differentiation of K562 cells. In this study, we characterized the signaling pathway of LT suppressed erythrocytic differentiation by Western blotting. Our results suggest that LT might suppress erythrocytic differentiation through blocking p38 pathway.

致謝------------------------------------------Ⅰ
中文摘要--------------------------------------Ⅱ
英文摘要--------------------------------------Ⅲ
目錄------------------------------------------Ⅳ
圖表目錄--------------------------------------Ⅴ
緒論------------------------------------------1
實驗假說與目的--------------------------------8
材料與方法------------------------------------10
結果------------------------------------------26
討論------------------------------------------41
圖表------------------------------------------45
附圖------------------------------------------78
參考文獻--------------------------------------85

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