PAG蛋白質對三氧化二砷誘發急性前骨髓性白血癌細胞毒性之角色研究; Role of PAG Protein in Arsenite Trioxide-Induced Acute Promyelocytic Leukemia Cell Apoptosis

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Title:	PAG蛋白質對三氧化二砷誘發急性前骨髓性白血癌細胞毒性之角色研究;Role of PAG Protein in Arsenite Trioxide-Induced Acute Promyelocytic Leukemia Cell Apoptosis
Authors:	王俊麟;Chin-Lin Wang
Contributors:	生命科學研究所
Keywords:	急性前骨髓性白血病;三氧化二砷;血癌;APL;NB4;As2O3;PAG
Date:	2001-07-08
Issue Date:	2009-09-22 10:16:43 (UTC+8)
Publisher:	國立中央大學圖書館
Abstract:	中文摘要砷化物是廣泛存在於自然環境中的毒性物質，跟人類皮膚癌、肺癌及肝癌的發生息息相關。最近的研究中指出，三氧化二砷能有效地應用於血癌的治療。報告中發現三氧化二砷是經由誘發過氧化氫相關路徑來造成急性前骨髓性白血癌細胞凋亡。TPX II為一過氧化酶，然而，TPX II在三氧化二砷誘發急性前骨髓性白血癌細胞凋亡之角色仍是未知的。本研究的目的是要探討TPX II在三氧化二砷誘發毒性之角色扮演。實驗結果顯示，以三氧化二砷處理NB4及K562兩株急性前骨髓性白血癌細胞，都會誘發TPX II的表現，且呈現時間相關性。因NB4細胞中的TPX II有明顯較低的表現量，故在處理三氧化二砷後，有較K562細胞高的過氧化氫累積。為了更進一步確定TPX II在三氧化二砷所誘發毒性之角色，故我們將哺乳類TPX II基因轉殖到NB4細胞 (NB4-PAG)。而NB4-PAG在處理三氧化二砷後，有較少的過氧化氫累積，且死亡情況降低。此外，同時以MS (glutathione peroxidase inhibitor)及三氧化二砷處理NB4-V及NB4-PAG細胞後，NB4-V細胞的過氧化氫累積及細胞凋亡均較無MS處理明顯增加許多，且在相同條件下，NB4-PAG細胞也能有效抑制三氧化二砷所誘導的過氧化氫累積及細胞凋亡的發生。這些結果顯示細胞中的TPX II可藉由降低過氧化氫累積來減少細胞凋亡。 Abstract Arsenic is a common environmental toxicant, which associated with human skin, lung and liver cancers. However, arsenic trioxide has also been employed recently in leukemia therapy. It has been found that arsenic trioxide treatment resulted in promyelocytic leukemia cell apoptosis via a hydrogen peroxide-dependent pathway. Although thioredoxin peroxidase II (TPX II) has been demonstrated to have hydrogen peroxidase function, the role of TPX in arsenic-induced apoptosis in leukemia remained unknown. The specific aims of this study is to explore the role of thioredoxin peroxidase II (TPX-II, a hydrogen peroxidase) in arsenic trioxide-induced toxicity. Arsenic trioxide treatment induces the expression of thioredoxin peroxidase II (TPX-II, a hydrogen peroxidase) in a time dependent manner in two acute myelocytic leukemia cells, NB4 and K562 cells. The NB4 cells were shown substantially lower levels of TPX-II, and hence higher H2O2 accumulation than that of K562 cells by the treatment of arsenic trioxide. To further explore the role of TPX II in arsenic trioxide-induced toxicity, the NB4 cells were transfected with cDNA encoding the mammalian TPX II proteins (NB4-PAG). The NB4-PAG cells were shown lower H2O2 accumulation and more resistant to death in response to arsenic trioxide treatment. Furthermore, co-treatment with mercaptosuccinic acid (MS, a glutathione peroxidase inhibitor) significantly enhanced the arsenic trioxide-induced H2O2 accumulation and apoptosis in NB4-V cells. Whilst the NB4-PAG cells were apparently accumulated less H2O2 and insensitive to apoptosis under the same treatment. These results suggest that TPX-II plays an important role in preventing cells from apoptosis by lowering intracellular H2O2 accumulation.
Appears in Collections:	[Graduate Institute of Life Science] Electronic Thesis & Dissertation

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