美國哈佛大學(xué)與匹茲堡大學(xué)的科學(xué)家,，首度的揭露出由細(xì)胞里粒腺體所調(diào)控，利用微量的一氧化碳 (Carbon Monoxide),，進(jìn)行身體抗發(fā)炎反應(yīng)的機(jī)制,，就這個(gè)新的發(fā)現(xiàn)來說，科學(xué)家有可能在未來,，利用這個(gè)原本會(huì)造成身體中毒的分子,，發(fā)展出新一代的抗發(fā)炎治療方法。
發(fā)炎身體所擁有的自然反應(yīng),，也是抵抗外來感染的一道防線,，當(dāng)身體有感染物入侵的時(shí)候，發(fā)炎反應(yīng)會(huì)立刻啟動(dòng),，快速的活化相關(guān)的免疫細(xì)胞,，而就進(jìn)行器官移殖的病人來說，發(fā)炎反應(yīng)的發(fā)生，反而會(huì)危及殖入器官的正常功能,，因此不當(dāng)?shù)陌l(fā)炎反應(yīng),，不管是急性的發(fā)炎或者是慢性的發(fā)炎，都有可能造成身體組織的傷害,，而就現(xiàn)階段來說,，臨床上控制發(fā)炎反應(yīng)的作法并非全然成功，這樣的結(jié)果使得探究發(fā)炎反應(yīng)的真正過程,，成為臨床研究一個(gè)很重要的目標(biāo),。
據(jù)了解這次由研究團(tuán)隊(duì)共同發(fā)表在 FASEB期刊上的論文指出，具有細(xì)胞內(nèi)分子引擎 (molecular engines)的粒線體 (mitochondria),，會(huì)和非常微量的一氧化碳反應(yīng),，因而釋放出適量的化學(xué)訊號(hào)分子來降低或者是關(guān)閉身體的不當(dāng)發(fā)炎反應(yīng)，目前就動(dòng)物模型的研究數(shù)據(jù)看來,，這個(gè)新發(fā)現(xiàn)有極大的可能,，成為新一代調(diào)控發(fā)炎反應(yīng)的藥物發(fā)展方向。
(資料來源 : Bio.com)
原始出處: http://www.bio.com/newsfeatures/newsfeatures_research.jhtml?cid=27600005
部分英文原文：
The FASEB Journal. 2007;21:1099-1106
Carbon monoxide signals via inhibition of cytochrome c oxidase and generation of mitochondrial reactive oxygen species
Brian S. Zuckerbraun*,1, Beek Yoke Chin, Martin Bilban, Joana de Costa d’Avila, Jayashree Rao*, Timothy R. Billiar* and Leo E. Otterbein
Departments of Surgery,
* University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA; and
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA
1Correspondence: University of Pittsburgh School of Medicine, NW653 MUH, 3459 Fifth Ave., Pittsburgh, PA 15213, USA. E-mail: [email protected]
Carbon monoxide (CO), which is produced endogenously in the breakdown of heme, has been recognized as an important physiological second messenger similar to NO. Additionally, pharmacological delivery of CO is protective in numerous models of injury, including ischemia/reperfusion, transplantation, hemorrhagic shock, and endotoxemia. However, the mechanism of action of CO is only partially elucidated focused primarily on how it modulates the cellular response to stress. The purpose of these investigations is to test the hypothesis that CO acts via inhibition of cytochrome c oxidase leading to the generation of low levels of reactive oxygen species (ROS) that in turn mediate subsequent adaptive signaling. We show here that CO increases ROS generation in RAW 264.7 cells, which is inhibited by antimycin A and is absent in respiration-deficient 0 cells. CO inhibits cytochrome c oxidase, while maintaining cellular ATP levels and increasing mitochondrial membrane potential. The addition of antioxidants or inhibition of complex III of the electron transport chain by antimycin A attenuates the inhibitory effects of CO on lipopolysaccharide (LPS)-induced TNF- and blocked CO-induced p38 MAPK phosphorylation, which we previously have shown to be important in the anti-inflammatory effects of CO.—Zuckerbraun, B. S., Chin, B. Y., Bilban, M., de Costa d’Avila, J., Rao, J., Billiar, T. R., Otterbein, L. E. Carbon monoxide signals via inhibition of cytochrome c oxidase and generation of mitochondrial reactive oxygen species.
Key Words: macrophage • p38 MAPK • tumor necrosis factor-alpha
