摘要
(SLs)调节细胞凋亡、增殖和压力反应。SLs,包括神经酰胺、糖鞘脂(葡萄糖基酰胺、乳糖基酰胺和神经节)和鞘氨-1-磷酸(S1P),在遗传(溶酶体储存疾病,先天性肾病综合征和多囊肾病)和非遗传性慢性肾脏疾病(CKDs)的发病机理和进展中起着重要作用。在CKDs中,SLs的代谢缺陷会导致并发症(心血管事件等)。在肾小球损伤和与CKDs相关的并发症的调节中,细胞凋亡和抗凋亡S1P的平衡作用是至关重要的。SLs、内皮功能和肾素血管紧张素-醛固酮系统(RAAS)的相互作用在肾小球损伤的调节中起着重要的作用。SLs影响线粒体功能调节线粒体通透性转换(MPT)的打开毛孔,线粒体外膜通透性(MOMP),生成的活性氧(ROS),和bcl - 2家族蛋白的表达,导致细胞色素c的释放和半胱天冬酶激活,导致细胞凋亡,调节肾小球细胞增殖或肾纤维化。本文回顾总结了当前SLs代谢缺陷的证据支持一个角色在肾小球损伤的发病和进展,并讨论了线粒体的作用,包括MPT毛孔,MOMP,ROS生成、bcl - 2家族蛋白质相互作用SLs,内皮功能和老城,SLs-induced下游信号事件半散装。这些因素之间的串扰在CKDs的发病机理和发展过程中起着重要的作用。摘要讨论了针对SLs代谢缺陷的酶调节代谢缺陷的治疗策略,并对其进行了讨论。
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
Current Medicinal Chemistry
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.
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Sphingolipids in Genetic and Acquired Forms of Chronic Kidney Diseases, Current Medicinal Chemistry 2017; 24 (12) . https://dx.doi.org/10.2174/0929867324666170112114525
DOI https://dx.doi.org/10.2174/0929867324666170112114525 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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