Quantitative proteomic analysis reveals the perturbation of multiple cellular pathways in HL-60 cells induced by arsenite treatment.
Quantitative proteomic analysis reveals the perturbation of multiple cellular pathways in HL-60 cells induced by arsenite treatment.
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DOI：
10.1021/pr9011359
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发表时间：
2010-02-05
影响因子：
4.4
通讯作者：
Wang, Yinsheng
中科院分区：
文献类型：
--
作者：
Xiong, Lei;Wang, Yinsheng
关键词：
砷在环境中无处不在；它是一种已知的人类致癌物，矛盾的是，它也是一种成功的药物，用于急性早幼粒细胞白血病（APL）的临床缓解。对亚砷酸盐处理诱导的细胞反应进行了多年的研究；然而，其细胞毒性和治疗活性的确切机制尚不清楚。在这里，我们报告了使用质谱法和细胞培养中氨基酸稳定同位素标记（SILAC）来比较研究未经处理或用临床相关浓度的亚砷酸盐处理的HL-60细胞中的蛋白质表达。我们的研究结果显示，在正向和反向SILAC测量中定量的1067个蛋白中，56个蛋白在亚砷酸盐处理下表达水平显著改变。核心组蛋白、中性粒细胞弹性酶、α-甘露糖苷酶表达上调，脂肪酸合成酶和蛋白磷酸酶1α表达下调。我们进一步证明，亚砷酸盐诱导的HL-60细胞生长抑制可以通过脂肪酸合酶的最终产物棕榈酸盐处理来恢复，这支持了亚砷酸盐发挥其细胞毒性作用，部分是通过抑制脂肪酸合酶的表达和抑制内源性脂肪酸的产生来实现的。本研究结果为深入了解亚砷酸盐的分子作用机制提供了重要的新知识。
Arsenic is ubiquitously present in the environment; it is a known human carcinogen and paradoxically it is also a successful drug for the clinical remission of acute promyelocytic leukemia (APL). The cellular responses induced by arsenite treatment have been investigated for years; however, the precise mechanisms underlying its cytotoxicity and therapeutic activity remain unclear. Here we report the use of mass spectrometry together with stable isotope labeling by amino acids in cell culture (SILAC) for the comparative study of protein expression in HL-60 cells that were untreated or treated with a clinically relevant concentration of arsenite. Our results revealed that, among the 1067 proteins quantified in both forward and reverse SILAC measurements, 56 had significantly altered levels of expression induced by arsenite treatment. These included the up-regulation of core histones, neutrophil elastase, α-mannosidase as well as the down-regulation of fatty acid synthase and protein phosphatase 1α. We further demonstrated that the arsenite-induced growth inhibition of HL-60 cells could be rescued by treatment with palmitate, the final product of fatty acid synthase, supporting that arsenite exerts its cytotoxic effect, in part, via suppressing the expression of fatty acid synthase and inhibiting the endogenous production of fatty acid. The results from the present study offered important new knowledge for gaining insights into the molecular mechanisms of action of arsenite.
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影响因子：
10.4
作者：
Morales, KH;Ryan, L;Chen, CJ
通讯作者：
Chen, CJ
影响因子：
5.3
作者：
Karapetian, RN;Evstafieva, AG;Vartapetian, AB
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影响因子：
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作者：
FUNABASHI, H;KAWAGUCHI, A;IWASAKI, S
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IWASAKI, S
DOI：
10.1016/s1383-5742(97)00009-4
发表时间：
1997-06-01
影响因子：
5.3
作者：
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通讯作者：
OstroskyWegman, P
影响因子：
4.1
作者：
Lau, ATY;He, QY;Chiu, JF
通讯作者：
Chiu, JF