Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappaB, and Akt in normal and malignant human mesothelial cells.
Raw single-wall carbon nanotubes induce oxidative stress and activate MAPKs, AP-1, NF-kappaB, and Akt in normal and malignant human mesothelial cells.
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DOI：
10.1289/ehp.10924
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发表时间：
2008-09
影响因子：
10.4
通讯作者：
Vallyathan V
中科院分区：
文献类型：
--
作者：
Pacurari M;Yin XJ;Zhao J;Ding M;Leonard SS;Schwegler-Berry D;Ducatman BS;Sbarra D;Hoover MD;Castranova V;Vallyathan V
单壁碳纳米管（SWCNTs）以其独特的物理化学和机械性能在医学和工业领域具有许多潜在的新应用。在对单壁碳纳米管的毒性、生物持久性、致病性和移位到胸膜下区域的能力进行初步调查之后，人们非常关注。这些结果迫使研究潜在的相互作用的单壁碳纳米管与间皮细胞。暴露于石棉是恶性间皮瘤的主要原因在80-90%的个人谁开发的疾病。由于间皮细胞是石棉诱导的分子变化介导的氧化剂连接的机制的主要靶细胞，我们使用正常间皮细胞和恶性间皮细胞的分子信号的改变，在商业制造的单壁碳纳米管。在本研究中，我们将间皮细胞暴露于单壁碳纳米管，并研究了活性氧（ROS）的产生、细胞活力、DNA损伤、组蛋白H2 AX磷酸化、多聚腺苷酸的活化。（ADP-核糖）聚合酶1（PARP-1）、细胞外信号调节激酶（ERK）、Jun N末端激酶（JNK）、蛋白质p38的刺激以及激活蛋白-1（AP-1）的激活，核因子κB（NF-κB）和蛋白丝氨酸-苏氨酸激酶（Akt）。暴露于SWCNT诱导ROS产生，增加细胞死亡，增强DNA损伤和H2 AX磷酸化，并以剂量依赖性方式激活PARP、AP-1、NF-κB、p38和Akt。这些事件概括了与石棉暴露相关的间皮瘤发展中的一些关键分子事件。这里报道的细胞和分子研究结果确实表明，单壁碳纳米管可以通过激活与氧化应激相关的分子信号传导在间皮细胞中引起潜在的不良细胞反应，这对于保证体内动物暴露研究具有足够的意义。
Single-wall carbon nanotubes (SWCNTs), with their unique physicochemical and mechanical properties, have many potential new applications in medicine and industry. There has been great concern subsequent to preliminary investigations of the toxicity, biopersistence, pathogenicity, and ability of SWCNTs to translocate to subpleural areas. These results compel studies of potential interactions of SWCNTs with mesothelial cells. Exposure to asbestos is the primary cause of malignant mesothelioma in 80–90% of individuals who develop the disease. Because the mesothelial cells are the primary target cells of asbestos-induced molecular changes mediated through an oxidant-linked mechanism, we used normal mesothelial and malignant mesothelial cells to investigate alterations in molecular signaling in response to a commercially manufactured SWCNT. In the present study, we exposed mesothelial cells to SWCNTs and investigated reactive oxygen species (ROS) generation, cell viability, DNA damage, histone H2AX phosphorylation, activation of poly(ADP-ribose) polymerase 1 (PARP-1), stimulation of extracellular signal-regulated kinase (ERKs), Jun N-terminal kinases (JNKs), protein p38, and activation of activator protein-1 (AP-1), nuclear factor κB (NF-κB), and protein serine-threonine kinase (Akt). Exposure to SWCNTs induced ROS generation, increased cell death, enhanced DNA damage and H2AX phosphorylation, and activated PARP, AP-1, NF-κB, p38, and Akt in a dose-dependent manner. These events recapitulate some of the key molecular events involved in mesothelioma development associated with asbestos exposure. The cellular and molecular findings reported here do suggest that SWCNTs can cause potentially adverse cellular responses in mesothelial cells through activation of molecular signaling associated with oxidative stress, which is of sufficient significance to warrant in vivo animal exposure studies.
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影响因子：
8
作者：
Altomare, DA;You, HH;Testa, JR
通讯作者：
Testa, JR
DOI：
10.1073/pnas.90.8.3299
发表时间：
1993-04-15
影响因子：
11.1
作者：
HEINTZ, NH;JANSSEN, YM;MOSSMAN, BT
通讯作者：
MOSSMAN, BT
影响因子：
11.2
作者：
Altomare, DA;Vaslet, CA;Testa, JR
通讯作者：
Testa, JR
影响因子：
--
作者：
Maynard, Andrew D.
通讯作者：
Maynard, Andrew D.
影响因子：
11.4
作者：
Roco, MC
通讯作者：
Roco, MC