Quinones and aromatic chemical compounds in particulate matter induce mitochondrial dysfunction: implications for ultrafine particle toxicity.
Quinones and aromatic chemical compounds in particulate matter induce mitochondrial dysfunction: implications for ultrafine particle toxicity.
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DOI：
10.1289/ehp.7167
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发表时间：
2004-10
影响因子：
10.4
通讯作者：
Nel A
中科院分区：
文献类型：
--
作者：
Xia T;Korge P;Weiss JN;Li N;Venkatesen MI;Sioutas C;Nel A
颗粒污染物通过产生氧化应激对健康造成不利影响。一个关键的问题是，这些影响是由颗粒物还是它们的化合物介导的。在这篇文章中，我们展示了从柴油废气颗粒（dep）中分离出来的脂肪族、芳香族和极性有机化合物在RAW 264.7细胞中发挥不同的毒性作用。细胞分析表明，富醌极性组分比富多环芳烃（PAH）极性组分在O2•−生成、膜电位降低（ΔΨm）、线粒体膜质量损失和诱导凋亡方面更有效。极性组分的主要作用是促进环孢素A （CsA）敏感的肝线粒体通透性过渡孔（PTP）的打开。这种开放效应依赖于低剂量时对PTP的直接影响，以及高剂量时钙（Ca2+）负载线粒体对ΔΨm的影响。直接的PTP效应由氧化还原循环DEP醌类模拟。虽然脂肪部分没有干扰线粒体功能，但芳香部分在低剂量下增加了Ca2+保留能力，并在高剂量下诱导线粒体肿胀和ΔΨm降低。这种膨胀效应主要是CsA不敏感的，可以由DEPs中存在的多环芳烃的混合物再现。这些对分离线粒体的化学作用可以通过完整的dep和环境超细颗粒（ufp）重现。相比之下，商业聚苯乙烯纳米颗粒未能发挥线粒体效应。这些结果表明，DEP和UFP对PTP和ΔΨm的影响是由吸附的化学物质介导的，而不是颗粒本身。
Particulate pollutants cause adverse health effects through the generation of oxidative stress. A key question is whether these effects are mediated by the particles or their chemical compounds. In this article we show that aliphatic, aromatic, and polar organic compounds, fractionated from diesel exhaust particles (DEPs), exert differential toxic effects in RAW 264.7 cells. Cellular analyses showed that the quinone-enriched polar fraction was more potent than the polycyclic aromatic hydrocarbon (PAH)–enriched aromatic fraction in O2•− generation, decrease of membrane potential (ΔΨm), loss of mitochondrial membrane mass, and induction of apoptosis. A major effect of the polar fraction was to promote cyclosporin A (CsA)–sensitive permeability transition pore (PTP) opening in isolated liver mitochondria. This opening effect is dependent on a direct effect on the PTP at low doses as well as on an effect on ΔΨm at high doses in calcium (Ca2+)-loaded mitochondria. The direct PTP effect was mimicked by redox-cycling DEP quinones. Although the aliphatic fraction failed to perturb mitochondrial function, the aromatic fraction increased the Ca2+ retention capacity at low doses and induced mitochondrial swelling and a decrease in ΔΨm at high doses. This swelling effect was mostly CsA insensitive and could be reproduced by a mixture of PAHs present in DEPs. These chemical effects on isolated mitochondria could be reproduced by intact DEPs as well as ambient ultrafine particles (UFPs). In contrast, commercial polystyrene nanoparticles failed to exert mitochondrial effects. These results suggest that DEP and UFP effects on the PTP and ΔΨm are mediated by adsorbed chemicals rather than the particles themselves.
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DOI：
10.1165/ajrcmb.25.1.4405
发表时间：
2001-07-01
影响因子：
6.4
作者：
Jyonouchi, H;Sun, SN;Cornfield, DN
通讯作者：
Cornfield, DN
影响因子：
10.4
作者：
Gurgueira SA;Lawrence J;Coull B;Murthy GG;González-Flecha B
通讯作者：
González-Flecha B
DOI：
10.1073/pnas.052713199
发表时间：
2002-03-05
影响因子：
11.1
作者：
Korge, P;Honda, HM;Weiss, JN
通讯作者：
Weiss, JN
影响因子：
2.9
作者：
MAJIMA, E;SHINOHARA, Y;TERADA, H
通讯作者：
TERADA, H
影响因子：
4.8
作者：
MAJIMA, E;IKAWA, K;TERADA, H
通讯作者：
TERADA, H