Metabolic shift in lung alveolar cell mitochondria following acrolein exposure
Metabolic shift in lung alveolar cell mitochondria following acrolein exposure
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DOI：
10.1152/ajplung.00165.2013
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发表时间：
2013-11-01
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.;Yin, Fei;Cadenas, Enrique
丙烯醛是一种α， β不饱和亲电试剂，是一种从柴油废气和食用油中释放到环境空气中的环境污染物。本研究探讨丙烯醛在改变线粒体功能和肺特异性细胞代谢中的作用。将RLE-6TN、H441和初级肺泡II型（pAT2）细胞暴露于丙烯醛4小时，通过XF细胞外通量分析研究丙烯醛对线粒体耗氧率的影响。低剂量丙烯醛暴露以剂量依赖的方式减少线粒体呼吸，因为在所有三种细胞类型中葡萄糖代谢的改变。丙烯醛抑制甘油醛-3-磷酸脱氢酶（GAPDH）活性，导致RLE-6TN、H441和pAT2细胞线粒体呼吸的底物利用率降低；GAPDH活性的降低在pAT2细胞中通过葡萄糖-6-磷酸脱氢酶活性的增加来补偿，葡萄糖-6-磷酸脱氢酶是戊糖磷酸途径的调节控制。葡萄糖代谢产生的丙酮酸减少导致利用替代来源来支持线粒体能量产生：棕榈酸- bsa复合物增加了RLE-6TN和pAT2细胞的线粒体呼吸。棕榈酸盐在肺泡细胞中用于表面活性剂的生物合成可能被证明是线粒体呼吸的替代燃料来源。因此，丙烯醛暴露后，肺泡细胞中磷脂酰胆碱水平下降，磷脂酶a(2)活性增加。这些发现有助于理解在暴露于环境毒物后肺功能改变的病理生理情况下经常观察到的表面活性剂水平下降。
Acrolein, an alpha,beta unsaturated electrophile, is an environmental pollutant released in ambient air from diesel exhausts and cooking oils. This study examines the role of acrolein in altering mitochondrial function and metabolism in lung-specific cells. RLE-6TN, H441, and primary alveolar type II (pAT2) cells were exposed to acrolein for 4 h, and its effect on mitochondrial oxygen consumption rates was studied by XF Extracellular Flux analysis. Low-dose acrolein exposure decreased mitochondrial respiration in a dose-dependent manner because of alteration in the metabolism of glucose in all the three cell types. Acrolein inhibited glyceraldehyde-3-phosphate dehydrogenase (GAPDH) activity, leading to decreased substrate availability for mitochondrial respiration in RLE-6TN, H441, and pAT2 cells; the reduced GAPDH activity was compensated in pAT2 cells by an increase in the activity of glucose-6-phosphate dehydrogenase, the regulatory control of the pentose phosphate pathway. The decrease in pyruvate from glucose metabolism resulted in utilization of alternative sources to support mitochondrial energy production: palmitate-BSA complex increased mitochondrial respiration in RLE-6TN and pAT2 cells. The presence of palmitate in alveolar cells for surfactant biosynthesis may prove to be the alternative fuel source for mitochondrial respiration. Accordingly, a decrease in phosphatidylcholine levels and an increase in phospholipase A(2) activity were found in the alveolar cells after acrolein exposure. These findings have implications for understanding the decrease in surfactant levels frequently observed in pathophysiological situations with altered lung function following exposure to environmental toxicants.