Nagle W A, Moss A J, Henle K J
Int J Radiat Biol Relat Stud Phys Chem Med. 1985 Nov;48(5):821-35. doi: 10.1080/09553008514551921.
The antibiotic pentalenolactone, a specific inhibitor of glyceraldehydephosphate dehydrogenase, was used to investigate the effect of glycolytic adenosine triphosphate (ATP) synthesis on the survival response of aerobic and hypoxic Chinese hamster cells treated with 42 degrees C hyperthermia. Data obtained with aerobic cells, incubated in balanced salt solutions supplemented with different substrates for ATP production, showed that 50 microM pentalenolactone blocked ATP synthesis via glycolysis but not by oxidative phosphorylation. The glycolytic inhibition was reversed upon transfer of the cells to antibiotic-free medium, and minimal cytotoxicity (less than 20 per cent) was observed. Hypoxic cultures were obtained by incubating dense cell suspensions (2 X 10(6)/ml) to produce metabolic oxygen depletion. Concomitant with the development of hypoxia, pentalenolactone-treated cells became ATP-depleted; cellular ATP levels were reduced by about 70-fold as compared to hypoxic cells in the antibiotic-free medium. The ATP-depleted cells were more sensitive to killing by hyperthermia. Comparison of the 42 degrees C survival curves for control and the antibiotic-treated hypoxic cells yielded a dose-modifying factor of 4 (5 per cent survival level). The results indicate that inhibition of glycolytic ATP synthesis, for example by pentalenolactone, can selectively sensitize hypoxic cells to the lethal effects of mild hyperthermia.
抗生素戊烯醇内酯是磷酸甘油醛脱氢酶的特异性抑制剂，被用于研究糖酵解三磷酸腺苷（ATP）合成对经42℃高温处理的需氧和缺氧中国仓鼠细胞存活反应的影响。在补充了不同ATP生成底物的平衡盐溶液中培养需氧细胞所获得的数据表明，50微摩尔的戊烯醇内酯可阻断通过糖酵解进行的ATP合成，但不会阻断氧化磷酸化过程。当将细胞转移至不含抗生素的培养基中时，糖酵解抑制作用被逆转，并且观察到最小的细胞毒性（小于20%）。通过培养致密细胞悬液（2×10⁶/毫升）以耗尽代谢性氧气来获得缺氧培养物。随着缺氧状态的发展，经戊烯醇内酯处理的细胞出现ATP耗尽；与不含抗生素培养基中的缺氧细胞相比，细胞内ATP水平降低了约70倍。ATP耗尽的细胞对高温杀伤更为敏感。对照和经抗生素处理的缺氧细胞在42℃下的存活曲线比较得出剂量修正因子为4（5%存活水平）。结果表明，例如通过戊烯醇内酯抑制糖酵解ATP合成，可选择性地使缺氧细胞对轻度高温的致死效应敏感化。
