Division of Nephrology, Department of Medicine, Massachusetts General Hospital, Boston, MA; Harvard Medical School, Boston, MA.
Harvard Medical School, Boston, MA; Division of Nephrology, Vascular Biology Research Center, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA; Surgical Immunotherapy at Roger Williams Medical Center, Providence, RI.
Semin Nephrol. 2017 Nov;37(6):546-551. doi: 10.1016/j.semnephrol.2017.07.008.
Apolipoprotein L1 (APOL1) protein is the human serum factor that protect human beings against Trypanosoma brucei brucei, the cause of trypanosomiasis. Subspecies of T b brucei that cause human sleeping sickness-T b gambiense and T b rhodesiense evolved molecular mechanisms that enabled them to evade killing by APOL1. Sequence changes (termed G1 and G2) in the APOL1 gene that restored its ability to kill T b rhodesiense also increase the risk of developing glomerular diseases and accelerate progression to end-stage kidney disease. To lyse trypanosome parasites, APOL1 forms pores in the trypanosome endolysosomal and mitochondrial membranes, resulting in rapid membrane depolarization. However, the molecular mechanism underlying APOL1 nephropathy is unknown. Recent experimental evidence has shown that aberrant efflux of intracellular potassium is an early event in APOL1-induced death of human embryonic kidney cells. Here, we discuss the possibility that abnormal efflux of cellular potassium or other cations may be relevant to the pathogenesis of APOL1 nephropathy.
载脂蛋白 L1（APOL1）蛋白是人类血清中的一种因子，可保护人类免受引起非洲锥虫病的布氏锥虫布鲁斯株的侵害。引起人类昏睡病的布氏锥虫亚种 T b 冈比亚和 T b 罗得西亚进化出了分子机制，使它们能够逃避 APOL1 的杀伤。APOL1 基因中的序列变化（称为 G1 和 G2）恢复了其杀伤 T b 罗得西亚的能力，同时也增加了肾小球疾病的风险，并加速了终末期肾病的进展。为了裂解锥虫寄生虫，APOL1 在锥虫内溶酶体和线粒体膜中形成孔，导致膜迅速去极化。然而，APOL1 肾病的分子机制尚不清楚。最近的实验证据表明，细胞内钾离子的异常外排是 APOL1 诱导人胚肾细胞死亡的早期事件。在这里，我们讨论了细胞内钾离子或其他阳离子的异常外排是否与 APOL1 肾病的发病机制有关。
