Short-term cigarette smoke exposure induces reversible changes in energy metabolism and cellular redox status independent of inflammatory responses in mouse lungs
Short-term cigarette smoke exposure induces reversible changes in energy metabolism and cellular redox status independent of inflammatory responses in mouse lungs
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DOI：
10.1152/ajplung.00219.2012
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发表时间：
2012-11-01
影响因子：
4.9
通讯作者：
Cadenas, Enrique
中科院分区：
文献类型：
--
作者：
Agarwal, Amit R.;Zhao, Liqin;Cadenas, Enrique
阿加瓦尔AR，赵L，桑切蒂H，孙达尔IK，拉赫曼I，卡德纳斯E。短期吸烟暴露可诱导小鼠肺能量代谢和细胞氧化还原状态发生可逆变化，且与炎症反应无关。《美国生理学杂志 - 肺细胞与分子生理学》303卷：L889 - L898，2012年。首次发表于2012年10月12日；doi:10.1152/ajplung.00219.2012。 - 吸烟会导致细胞氧化还原状态改变，这是慢性阻塞性肺疾病发病机制的一个标志。本研究探讨了吸烟（CS）暴露在能量代谢损伤以及随之而来的线粒体功能障碍中的作用。雄性A/J小鼠暴露于吸烟机产生的烟雾中4周或8周。一个恢复组暴露于烟雾中8周，然后恢复2周。急性吸烟暴露改变了肺葡萄糖代谢，导致糖酵解速率降低和磷酸戊糖途径增加，这分别通过甘油醛 - 3 - 磷酸脱氢酶（GAPDH）和葡萄糖 - 6 - 磷酸脱氢酶表达及活性的改变得以证明。发现GAPDH的损伤是由于其催化位点半胱氨酸的谷胱甘肽化。代谢变化与细胞和线粒体氧化还原状态的变化相关，这些变化通过吡啶核苷酸和谷胱甘肽来评估。吸烟暴露引起复合物II、III、IV和V的表达上调以及复合物II、IV和V的活性上调。对暴露于烟雾中8周的小鼠肺基因表达进行的微阵列分析显示，一组涉及代谢、电子传递链、氧化磷酸化、线粒体运输和动力学以及氧化还原调节的基因上调。这些变化的发生与炎症反应无关。这些发现对急性肺暴露于烟雾时能量和氧化还原代谢改变的早期发生具有启示意义。
Agarwal AR, Zhao L, Sancheti H, Sundar IK, Rahman I, Cadenas E. Short-term cigarette smoke exposure induces reversible changes in energy metabolism and cellular redox status independent of inflammatory responses in mouse lungs. Am J Physiol Lung Cell Mol Physiol 303: L889-L898, 2012. First published October 12, 2012; doi: 10.1152/ajplung.00219.2012.-Cigarette smoking leads to alteration in cellular redox status, a hallmark in the pathogenesis of chronic obstructive pulmonary disease. This study examines the role of cigarette smoke (CS) exposure in the impairment of energy metabolism and, consequently, mitochondrial dysfunction. Male A/J mice were exposed to CS generated by a smoking machine for 4 or 8 wk. A recovery group was exposed to CS for 8 wk and allowed to recover for 2 wk. Acute CS exposure altered lung glucose metabolism, entailing a decrease in the rate of glycolysis and an increase in the pentose phosphate pathway, as evidenced by altered expression and activity of GAPDH and glucose-6-phosphate dehydrogenase, respectively. Impairment of GAPDH was found to be due to glutathionylation of its catalytic site cysteines. Metabolic changes were associated with changes in cellular and mitochondrial redox status, assessed in terms of pyridine nucleotides and glutathione. CS exposure elicited an upregulation of the expression of complexes II, III, IV, and V and of the activity of complexes II, IV, and V. Microarray analysis of gene expression in mouse lungs after exposure to CS for 8 wk revealed upregulation of a group of genes involved in metabolism, electron transfer chain, oxidative phosphorylation, mitochondrial transport and dynamics, and redox regulation. These changes occurred independently of inflammatory responses. These findings have implications for the early onset of alterations in energy and redox metabolism upon acute lung exposure to CS.