Single-walled carbon nanotubes alter cytochrome c electron transfer and modulate mitochondrial function.
Single-walled carbon nanotubes alter cytochrome c electron transfer and modulate mitochondrial function.
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DOI：
10.1021/nn302457v
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发表时间：
2012-12-21
期刊：
影响因子：
17.1
通讯作者：
Liang, Xing-Jie
中科院分区：
文献类型：
--
作者：
Ma, Xiaowei;Zhang, Li-Hua;Wang, Li-Rong;Xue, Xue;Sun, Ji-Hong;Wu, Yan;Zou, Guozhang;Wu, Xia;Wang, Paul C.;Wamer, Wayne G.;Yin, Jun-Jie;Zheng, Kaiyuan;Liang, Xing-Jie
关键词：
单壁碳纳米管（SWCNTs）由于其独特的物理化学性质，被广泛用于各种生物医学应用，如药物输送、体内成像和癌症光热治疗。然而，一旦它们进入细胞，SWCNTs对胞内细胞器和大分子的作用尚不完全清楚。细胞色素c （Cyt c）是线粒体中电子传递链的关键组成部分，在细胞能量消耗、生长和分化过程中起着至关重要的作用。在本研究中，我们发现经SWCNTs处理的人上皮KB细胞线粒体膜电位（MMP）和线粒体摄氧量大大降低，同时伴有Cyt c的减少。SWCNTs以pH依赖的方式脱氧Cyt c，这可以从550 nm特征吸收峰的出现中得到证明，该吸收峰的强度随着pH的增加而增加。圆二色性测量证实了ph依赖性构象变化，这促进了SWCNTs与Cyt c血红素口袋的更紧密结合，从而加速了Cyt c的还原。通过电子自旋共振光谱测量，SWCNTs也干扰了Cyt c的电子转移。综上所述，由于Cyt c的电子转移减弱和构象改变，SWCNTs处理影响了Cyt c的氧化还原活性，从而改变了SWCNTs处理细胞的线粒体呼吸。这项工作对SWCNTs研究具有重要意义，因为它为SWCNTs对线粒体的破坏提供了新的认识，并对SWCNTs的生物医学应用具有重要意义。
Single-walled carbon nanotubes (SWCNTs) are broadly used for various biomedical applications such as drug delivery, in vivo imaging and cancer photothermal therapy due to their unique physiochemical properties. However, once they enter the cells, the effects of SWCNTs to the intracellular organelles and macromolecules are not comprehensively understood. Cytochrome c (Cyt c), as a key component of the electron transport chain in mitochondria, plays an essential role in cellular energy consumption, growth and differentiation. In this study, we found the mitochondrial membrane potential (MMP) and mitochondrial oxygen uptake were greatly decreased in human epithelial KB cells treated with SWCNTs, which accompanies the reduction of Cyt c. SWCNTs deoxidized Cyt c in a pH dependent manner as evidenced by the appearance of a 550 nm characteristic absorption peak, which intensity increased as pH increase. Circular dichroism measurement confirmed the pH-dependent conformational change, which facilitated closer association of SWCNTs with the heme pocket of Cyt c and thus expedited the reduction of Cyt c. The electron transfer of Cyt c is also disturbed by SWCNTs, as measured with electron spin resonance spectroscopy. In conclusion, the redox activity of Cyt c was affected by SWCNTs treatment due to attenuated electron transfer and conformational change of Cyt c, which consequently changed mitochondrial respiration of SWCNTs treated cells. This work is significant to SWCNTs research because it provided novel understanding to the disruption of SWCNTs to the mitochondria and has important implications for biomedical applications of SWCNTs.
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