Damonte G, Guida L, Sdraffa A, Benatti U, Melloni E, Forteleoni G, Meloni T, Carafoli E, De Flora A
Institute of Biochemistry, University of Genoa, Italy.
Cell Calcium. 1992 Nov;13(10):649-58. doi: 10.1016/0143-4160(92)90075-4.
Favism is an acute hemolytic anemia triggered by ingestion of fava beans in genetically susceptible subjects with severe deficiency of glucose-6-phosphate dehydrogenase (G6PD) activity. Erythrocytes from 10 favic patients had constantly and markedly increased calcium levels, as compared with values detected in 4 asymptomatic G6PD-deficient controls. Correspondingly, the calcium permeability of erythrocytes, estimated as the fraction of intracellular calcium exchangeable with externally added 45Ca2+, was invariably enhanced in favism and returned to normal patterns after several months from the acute hemolytic crisis. In favic patients, the levels of erythrocyte calcium ATPase activities showed wide variability, ranging from 2.0-12.9 mumol Pi/ml RBC/h, while control values in asymptomatic G6PD-deficient subjects were 10.62 +/- 2.03 mumol Pi/ml RBC/h. Analysis of the calcium ATPase in situ in erythrocyte membranes from favic patients showed the same molecular mass of 134 kD as observed in the control subjects. Exposure of G6PD-deficient erythrocytes in vitro to autoxidizing divicine, a pyrimidine aglycone strongly implicated in the pathogenesis of favism which leads to late accumulation of intracellular calcium, caused: (i) a marked inactivation of calcium ATPase, without changes in the molecular mass of 134 kD; and (ii) the concomitant loss of spectrin, band 3 and band 4.1, all known substrates of the calcium activated procalpain-calpain proteolytic system. Thus, the increased intraerythrocytic calcium apparently results in the degradation of calcium ATPase observed in some favic patients. It is proposed that both enhanced calcium permeability and a calcium-stimulated degradation of the calcium pump are the mechanisms responsible for the perturbation of erythrocyte calcium homeostasis in favism.
蚕豆病是一种急性溶血性贫血，由严重缺乏葡萄糖-6-磷酸脱氢酶（G6PD）活性的遗传易感性个体摄入蚕豆引发。与4名无症状G6PD缺乏对照者检测到的值相比，10例蚕豆病患者的红细胞钙水平持续且显著升高。相应地，红细胞的钙通透性（以与外部添加的45Ca2+可交换的细胞内钙分数估算）在蚕豆病中总是增强，并在急性溶血危机数月后恢复正常模式。在蚕豆病患者中，红细胞钙ATP酶活性水平显示出很大差异，范围为2.0 - 12.9 μmol Pi/ml RBC/h，而无症状G6PD缺乏受试者的对照值为10.62 ± 2.03 μmol Pi/ml RBC/h。对蚕豆病患者红细胞膜原位钙ATP酶的分析显示，其分子量与对照受试者中观察到的134 kD相同。体外将G6PD缺乏的红细胞暴露于自氧化的异胺基巴比妥酸（一种与蚕豆病发病机制密切相关的嘧啶苷元，可导致细胞内钙的晚期积累），会导致：（i）钙ATP酶显著失活，分子量134 kD无变化；（ii）血影蛋白、带3和带4.1同时丢失，这些都是钙激活的钙蛋白酶原 - 钙蛋白酶蛋白水解系统的已知底物。因此，红细胞内钙增加显然导致了一些蚕豆病患者中观察到的钙ATP酶降解。有人提出，钙通透性增强和钙泵的钙刺激降解都是导致蚕豆病中红细胞钙稳态紊乱的机制。
