Involvement of MAPK proteins in bystander effects induced by chemicals and ionizing radiation
Involvement of MAPK proteins in bystander effects induced by chemicals and ionizing radiation
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DOI：
10.1016/j.mrfmmm.2009.12.007
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发表时间：
2010-04-01
影响因子：
2.3
通讯作者：
Tucker, James D.
中科院分区：
文献类型：
--
作者：
Asur, Rajalakshmi;Balasubramaniam, Mamtha;Tucker, James D.
许多研究已经检查了电离辐射引起的旁观者效应，但是很少有研究评估化学品引起类似效应的能力。我们之前报道了两种化学物质丝裂霉素C（MMC）和腐草霉素（PHL）在正常人类淋巴母细胞系中诱导旁观者效应的能力。本研究的重点是确定MAPK蛋白参与物理和化学DNA损伤剂诱导的旁观者效应，并评估MAPK抑制对旁观者诱导的caspase 3/7激活的影响。MAPK蛋白ERK 1/2，JNK和p38的磷酸化水平，从1至24小时后直接或旁观者暴露于MMC，PHL或辐射测量。我们观察到短暂的磷酸化，在早期的时间点，所有3种蛋白质在旁观者细胞。我们还评估了MAPK抑制对旁观者诱导的caspase 3/7活性的影响，以确定MAPK蛋白在旁观者诱导的细胞凋亡中的作用。我们观察到旁观者诱导的旁观者细胞caspase 3/7的激活。MAPK蛋白的抑制导致在早期时间点caspase 3/7活性降低，并且caspase活性在12和24 h之间增加（在ERK抑制的情况下）或恢复到基础水平（在JNK或p38抑制的情况下）。PHL被认为是一种拟辐射剂，然而在本研究中，PHL在MAPK磷酸化方面表现得更像一种化学物质而不像辐射。这些结果表明，MAPK蛋白参与辐射和化学物质诱导的旁观者效应，并提供了额外的证据表明，这种反应不仅限于辐射，而是细胞中的一种普遍的应激反应。C 2009 Elsevier B. V.保留所有权利。
Many studies have examined bystander effects induced by ionizing radiation, however few have evaluated the ability of chemicals to induce similar effects. We previously reported the ability of two chemicals, mitomycin C (MMC) and phleomycin (PHL) to induce bystander effects in normal human lymphoblastoid cell lines. The focus of the current study was to determine the involvement of the MAPK proteins in bystander effects induced by physical and chemical DNA damaging agents and to evaluate the effects of MAPK inhibition on bystander-induced caspase 3/7 activation. The phosphorylation levels of the MAPK proteins ERK1/2, JNK, and p38, were measured from 1 to 24 h following direct or bystander exposure to MMC, PHL or radiation. We observed transient phosphorylation, at early time points, of all 3 proteins in bystander cells. We also evaluated the effect of MAPK inhibition on bystander-induced caspase 3/7 activity to determine the role of MAPK proteins in bystander-induced apoptosis. We observed bystanderinduced activation of caspase 3/7 in bystander cells. Inhibition of MAPK proteins resulted in a decrease in caspase 3/7 activity at the early time points, and the caspase activity increased (in the case of ERK inhibition) or returned to basal levels (in the case of JNK or p38 inhibition) between 12 and 24 h. PHL is considered to be a radiomimetic agent, however in the present study PHL behaved more like a chemical and not like radiation in terms of MAPK phosphorylation. These results point to the involvement of MAPK proteins in the bystander effect induced by radiation and chemicals and provide additional evidence that this response is not limited to radiation but is a generalized stress response in cells. C 2009 Elsevier B.V. All rights reserved.