Slyshenkov Vyacheslav S, Dymkowska Dorota, Wojtczak Lech
Nencki Institute of Experimental Biology, Pasteura 3, 02-093 Warsaw, Poland.
FEBS Lett. 2004 Jul 2;569(1-3):169-72. doi: 10.1016/j.febslet.2004.05.044.
We have previously observed (summarized in BioFactors 17 (2003) 61) that pantothenic acid, pantothenol and other derivatives that are precursors of CoA protect cells and whole organs against peroxidative damage by increasing the content of cell glutathione. The present investigation was aimed to elucidate the mechanism of this increase in human lymphoblastoic (Jurkat) cells. It showed that incubation of the cells with pantothenic acid or pantothenol increased mainly the content of free glutathione, with little effect on protein-bound glutathione. Buthionine sulfoximine, an inhibitor of glutathione synthesis, prevented this increase. Increase of the content of free glutathione, as produced by pantothenic acid or pantothenol, was largely prevented by respiratory chain inhibitor rotenone, inhibitor of mitochondrial ATP synthesis oligomycin and uncoupler of oxidative phosphorylation of carbonyl cyanide 3-chlorophenylhydrazone. These treatments also decreased the cellular content of ATP. Preincubation with pantothenic acid or pantothenol also increased cell respiration with pyruvate as the exogenous substrate. Although no significant increase of total cell CoA content could be found, it is concluded that the increase of the glutathione level was due to increased production of ATP that was, in turn, a result of the increased content of mitochondrial CoA.
我们之前已经观察到（总结于《生物因子》17卷（2003年）第61页），泛酸、泛醇以及其他作为辅酶A前体的衍生物，通过增加细胞内谷胱甘肽的含量来保护细胞和整个器官免受过氧化损伤。本研究旨在阐明人类淋巴母细胞（Jurkat细胞）中这种增加的机制。研究表明，用泛酸或泛醇孵育细胞主要增加了游离谷胱甘肽的含量，而对蛋白结合型谷胱甘肽影响较小。谷胱甘肽合成抑制剂丁硫氨酸亚砜胺可阻止这种增加。泛酸或泛醇所导致的游离谷胱甘肽含量增加，在很大程度上被呼吸链抑制剂鱼藤酮、线粒体ATP合成抑制剂寡霉素以及羰基氰3-氯苯腙氧化磷酸化解偶联剂所阻止。这些处理也降低了细胞内ATP的含量。用泛酸或泛醇预孵育也增加了以丙酮酸作为外源底物时的细胞呼吸。尽管未发现细胞辅酶A总含量有显著增加，但可以得出结论，谷胱甘肽水平的增加是由于ATP生成增加，而这又是线粒体辅酶A含量增加的结果。
