Dysregulated Calcium Homeostasis and Oxidative Stress in Chronic Myeloid Leukemia (CML) Cells
Dysregulated Calcium Homeostasis and Oxidative Stress in Chronic Myeloid Leukemia (CML) Cells
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DOI：
10.1002/jcp.22140
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发表时间：
2010-08-01
影响因子：
5.6
通讯作者：
Giordano, Antonio
中科院分区：
文献类型：
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作者：
Ciarcia, Roberto;d'Angelo, Danila;Giordano, Antonio
慢性粒细胞白血病(CML)是一种由bcr-Abl蛋白致癌活性引起的造血干细胞疾病，bcr-Abl蛋白是一种去调节的酪氨酸激酶。钙可以直接作用于细胞酶，并与其他细胞代谢物，如环核苷酸，一起调节细胞功能。胞浆内钙离子浓度的改变与细胞分泌、收缩和细胞增殖的启动有关，而活性氧物种(ROS)的产生通过激活生长相关的信号通路与正常的细胞增殖相关。在这项研究中，我们在CML患者的外周血白细胞中评估了细胞内钙和氧化应激之间的平衡在CML疾病中的作用，以确定受这种病理影响的患者的可能治疗靶点。我们的结果表明，CML患者外周血单个核细胞在给予InSP(3)以及ATP和离子霉素(IONO)后，细胞内[Ca~(2+)](I)通量均下降。CML患者外周血中超氧化物歧化酶(SOD)活性明显降低，丙二醛(MDA)水平显著升高。最后，我们发现白藜芦醇能够下调InsP3和ATP对CML细胞内[Ca~(2+)](I)通量的影响，以及ATP和IONO对氧化应激的影响。J.细胞。物理。224：443-453,2010。(C)2010年Wiley-Liss公司
Chronic myeloid leukemia (CML) is a hematopoietic stem cell disorder caused by the oncogenic activity of the Bcr-Abl protein, a deregulated tyrosine kinase. Calcium may act directly on cellular enzymes and in conjunction with other cellular metabolites, such as cyclic nucleotides, to regulate cell functions. Alteration in the ionized calcium concentration in the cytosol has been implicated in the initiation of secretion, contraction, and cell proliferation as well as the production of reactive oxygen species (ROS) has been correlates with normal cell proliferation through activation of growth-related signaling pathways. In this study we evaluated in peripheral blood leukocytes from CML patients the role of the balance between intracellular calcium and oxidative stress in CML disease in order to identify possible therapeutic targets in patients affected by this pathology. Our results demonstrated that peripheral blood mononuclear cells derived from CML patients displayed decreased intracellular calcium [Ca2+](i) fluxes both after InsP(3) as well as ATP and ionomycin (IONO) administration. CML cells showed lower levels of superoxide dismutase (SOD) activity and significantly higher malondialdehyde levels (MDA) than peripheral blood mononuclear cells derived from control patients. Finally we showed that resveratrol is able to down-regulate InsP3 and ATP effects on intracellular calcium [Ca2+](i) fluxes as well as the effects of ATP and IONO on oxidative stress in CML cells. J. Cell. Physiol. 224: 443-453, 2010. (C) 2010 Wiley-Liss, Inc.