SLs在遗传和获取慢性肾脏疾病的作用

Title:Sphingolipids in Genetic and Acquired Forms of Chronic Kidney Diseases

Volume: 24 Issue: 12

关键词: 细胞凋亡，bcl-2家族蛋白，神经酰胺，肾小球损伤，线粒体，活性氧物种，肾素-血管紧张素-醛固酮系统，鞘氨-1磷酸盐

摘要: Sphingolipids (SLs) regulate apoptosis, proliferation, and stress response. SLs, including ceramide, glycosphingolipids (glucosylceramide, lactosylceramide, and gangliosides) and sphingosine-1-phosphate (S1P), play a role in the pathogenesis and progression of genetic (lysosomal storage disease, congenital nephrotic syndrome and polycystic kidney disease) and non-genetic forms of chronic kidney diseases (CKDs). SLs metabolism defects promote complications (cardiovascular events, etc.) via oxidant stress in CKDs. A balancing role of apoptotic SLs and anti-apoptotic S1P is crucial in the regulation of glomerular injury and complications associated with CKDs. Interaction between SLs, endothelial function and reninangiotensin- aldosterone system (RAAS) plays an important role in the regulation of glomerular injury. SLs affect mitochondrial function that regulate the opening of mitochondrial permeability transition (MPT) pore, mitochondrial outer membrane permeability (MOMP), generation of reactive oxygen species (ROS), and expression of BcL-2 family proteins, which result in cytochrome c release and caspase activation, leading to apoptosis, and regulate glomerular cell proliferation or renal fibrosis. This review article summarizes the current evidence supporting a role of SLs metabolism defects in the pathogenesis and progression of glomerular injury and discusses a role of mitochondria, including MPT pore, MOMP, ROS generation, BcL-2 family proteins, interaction between SLs, endothelial function and RAAS, and SLs-induced downstream signaling events in CKDs. Crosstalk between these factors plays a role in the pathogenesis and progression of CKDs. Therapeutic strategy of targeting SLs metabolism defects for CKDs through modulation of the enzymes responsible for SLs metabolism defects is also discussed.

Cite this article as:

Sphingolipids in Genetic and Acquired Forms of Chronic Kidney Diseases, Current Medicinal Chemistry 2017; 24 (12) . https://dx.doi.org/10.2174/0929867324666170112114525