Title:Sphingolipids in Genetic and Acquired Forms of Chronic Kidney Diseases
Volume: 24
Issue: 12
Author(s): Norishi Ueda*
Affiliation:
- Department of Pediatrics, Public Central Hospital of Matto Ishikawa, 3-8 Kuramitsu, Hakusan, 924-8588 Ishikawa,Japan
Keywords:
Apoptosis, Bcl-2 family proteins, ceramide, glomerular injury, mitochondria, reactive oxygen species,
renin-angiotensin-aldosterone system, sphingosine-1 phosphate
Abstract: 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.
