Mølstad P, Bøhmer T
Biochim Biophys Acta. 1981 Feb 20;641(1):71-8. doi: 10.1016/0005-2736(81)90569-1.
Diphtheria toxin added to the incubation medium reduced the rate of uptake and increased the efflux of L-[3H]carnitine in an established cell line from human heart (CCL 27, Girardi human heart cells). This resulted in a decrease in the level of intracellular carnitine to about 55% of control after exposure to 10(-8) mol/l diphtheria toxin for 24 h. As expected, a decrease in protein synthesis was found to be caused by the toxin, and this inhibition seemed to a large extent to antedate the alterations in the transport processes. Measurement of the kinetic parameters for the mechanism of uptake of L-[3H]carnitine revealed a reduction in V with unaltered Km after exposure to the toxin. We therefore suggest that diphtheria toxin imposes its effect on carnitine transport by inhibiting the synthesis of carriers. Prednisolone in the medium along with the toxin opposed its effect both on the uptake and efflux mechanism, but not on the inhibition of protein synthesis. Still, the decline in the intracellular level of carnitine was prevented by the corticoid hormone. Such a decline, accompanied by accumulation of triacyglycerols, occurs during the course of a diphtheric myocarditis. It is possible that prednisolone, by counteracting the effects of diphtheria toxin on the carnitine transport processes, could be beneficial in the treatment of this condition.
在人心脏来源的已建细胞系（CCL 27，吉拉尔迪人心肌细胞）的孵育培养基中加入白喉毒素，会降低L-[3H]肉碱的摄取速率并增加其外流。暴露于10^(-8) mol/L白喉毒素24小时后，细胞内肉碱水平降至对照水平的约55%。正如预期的那样，发现毒素会导致蛋白质合成减少，而且这种抑制在很大程度上早于转运过程的改变。对L-[3H]肉碱摄取机制的动力学参数进行测量发现，暴露于毒素后V降低而Km不变。因此，我们认为白喉毒素通过抑制载体的合成对肉碱转运产生影响。培养基中的泼尼松龙与毒素一起使用时，会对抗其对摄取和外流机制的影响，但不会对抗对蛋白质合成的抑制。不过，皮质激素可防止细胞内肉碱水平下降。在白喉性心肌炎病程中会出现这种伴随着三酰甘油积累的下降。泼尼松龙可能通过抵消白喉毒素对肉碱转运过程的影响，从而对这种病症的治疗有益。
