Schultheiss H P, Schulze K, Dörner A
Benjamin Franklin Hospital, Free University, Berlin, Germany.
Mol Cell Biochem. 1996 Oct-Nov;163-164:319-27. doi: 10.1007/BF00408672.
We found recently autoantibodies against the adenine nucleotide translocator (ANT), a carrier in the inner mitochondrial membrane, in sera of patients with myocarditis and dilated cardiomyopathy. To elucidate whether these antibodies are of pathophysiological importance, we investigated the function and expression of the adenine nucleotide translocator (ANT) in the heart muscle tissue of patients suffering from myocarditis and DCM. We found a markedly lowered transport capacity of the translocator accompanied by an elevation in total ANT protein content. The alteration in ANT protein amount is caused by an ANT isoform shift characterized by an increase in ANT 1 isoform protein associated with a decrease in ANT 2 isoform and an unchanged ANT 3 content. It could be shown that the isoform shift is not a progressive process during the disease period but an event in the early period of illness which becomes permanent. Simulating the effect of pathogenetic factors of autoimmunological diseases, we infected A/J mice with the enterovirus Coxsackie B3 and immunized guinea pigs with myocardial ANT protein. Both treatments led to autoimmunological responds and to a lowered myocardial transport capacity of ANT, to a disturbed energy metabolism and consequently to a depression of heart function.
我们最近在心肌炎和扩张型心肌病患者的血清中发现了针对腺嘌呤核苷酸转运体（ANT）的自身抗体，ANT是线粒体内膜上的一种载体。为了阐明这些抗体是否具有病理生理学重要性，我们研究了心肌炎和扩张型心肌病患者心肌组织中腺嘌呤核苷酸转运体（ANT）的功能和表达。我们发现转运体的转运能力显著降低，同时ANT总蛋白含量升高。ANT蛋白量的改变是由ANT同工型转变引起的，其特征是ANT 1同工型蛋白增加，ANT 2同工型减少，ANT 3含量不变。可以证明，同工型转变在疾病期间不是一个渐进的过程，而是疾病早期发生的一个事件，并会持续存在。模拟自身免疫性疾病致病因素的作用，我们用肠道病毒柯萨奇B3感染A/J小鼠，并用心肌ANT蛋白免疫豚鼠。两种处理均导致自身免疫反应，心肌ANT转运能力降低，能量代谢紊乱，进而导致心脏功能抑制。
