Instituto de Fisiología Celular, Departamento de Biología Celular y Desarrollo, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City 04510, DF, Mexico.
Instituto de Fisiología Celular, Departamento de Biología Celular y Desarrollo, Universidad Nacional Autónoma de México, Ciudad Universitaria, Mexico City 04510, DF, Mexico.
Free Radic Biol Med. 2013 Dec;65:1090-1100. doi: 10.1016/j.freeradbiomed.2013.08.176. Epub 2013 Aug 29.
In experimentally induced chronic gastritis, a compensatory mucosal cell proliferation occurs with enhanced glucose oxidative metabolism linked to lipoperoxidative events. Therefore, this study was aimed at assessing the participation of cell NAD/NADH redox state and mitochondrial functions during gastric mucosa proliferation and the effects of in vivo α-tocopherol (vitamin E) administration. Glucose oxidation and oxygen consumption were tested in gastric mucosa samples obtained from rats with gastritis and from those also treated with α-tocopherol. Gastric mucosal mitochondria were isolated and structural and functional parameters were determined. Succinate oxidation, ADP phosphorylation, mitochondrial enzyme activities, and membrane lipid composition were measured. In addition, parameters indicative of cellular NAD/NADH redox state, proliferation, apoptosis, and nitric oxide (NO) metabolism were also determined. After ethanol withdrawal, the damaged gastric mucosa increased glucose and oxygen consumption, events associated with a more reduced cytoplasmic NAD/NADH ratio. Enhanced mitochondrial oxidative phosphorylation and increased mitochondrial enzyme activities occurred early, accompanied by recovery of lost mitochondrial protein and lipid composition in the gastric mucosa, events associated with increased NO production. When mitochondrial function and structural events were normalized, apoptosis was initiated as assessed by the mitochondrial Bax/Bcl2 ratio. Treatment with α-tocopherol inhibited cell proliferation and blocked enhanced glucose utilization, mitochondrial substrate oxidation, and changes in redox state, delaying the onset of these adaptive metabolic changes, whereas it inhibited cell proliferation. In conclusion, α-tocopherol could abolish damage-induced "stress" signaling by desynchronizing mitochondrial adaptive responses, including mitochondria biogenesis, and consequently NAD/NADH redox, which seems to regulate gastric mucosal cell proliferation.
在实验性诱导的慢性胃炎中，发生补偿性黏膜细胞增殖，伴随着与脂质过氧化事件相关的葡萄糖氧化代谢增强。因此，本研究旨在评估细胞 NAD/NADH 氧化还原状态和线粒体功能在胃黏膜增殖过程中的参与作用，以及体内α-生育酚（维生素 E）给药的影响。在从胃炎大鼠和也用α-生育酚治疗的大鼠获得的胃黏膜样本中测试了葡萄糖氧化和耗氧量。分离胃黏膜线粒体并确定结构和功能参数。测量琥珀酸氧化、ADP 磷酸化、线粒体酶活性和膜脂质组成。此外，还测定了细胞 NAD/NADH 氧化还原状态、增殖、凋亡和一氧化氮（NO）代谢的指示参数。在乙醇戒断后，受损的胃黏膜增加了葡萄糖和耗氧量，这些事件与细胞质 NAD/NADH 比率的降低有关。早期发生增强的线粒体氧化磷酸化和增加的线粒体酶活性，伴随着胃黏膜中丢失的线粒体蛋白和脂质组成的恢复，这与 NO 产生的增加有关。当线粒体功能和结构事件正常化时，通过线粒体 Bax/Bcl2 比值评估了凋亡的启动。α-生育酚的治疗抑制了细胞增殖并阻止了增强的葡萄糖利用、线粒体底物氧化和氧化还原状态的变化，从而延迟了这些适应性代谢变化的发生，同时抑制了细胞增殖。总之，α-生育酚可以通过使线粒体适应性反应失去同步，包括线粒体生物发生，从而消除损伤诱导的“应激”信号，这似乎调节胃黏膜细胞增殖。
