ABSTRACT
Jiang et al. show that zinc finger FYVE-type containing 21, a Rab5 effector in glomerular endothelial cells is involved in the maintenance of glomerular filtration barrier homeostasis through the stabilization of activated endothelial nitric oxide synthase on subcellular vesicles. The study demonstrates that zinc finger FYVE-type containing 21 could modulate the levels of caveolin-1 in glomerular endothelial cells using vesicle-based trafficking, thereby supporting endothelial nitric oxide synthase activity. The authors provide evidence that decreased zinc finger FYVE-type containing 21 expression in glomerular endothelial cells could play a role in aging-related glomerular filtration barrier dysfunction.
Subject(s)
Aging , Caveolin 1 , Endothelial Cells , Nitric Oxide Synthase Type III , Aging/metabolism , Aging/physiology , Humans , Nitric Oxide Synthase Type III/metabolism , Caveolin 1/metabolism , Endothelial Cells/metabolism , Endothelial Cells/pathology , Animals , Glomerular Filtration Barrier/metabolism , Kidney Glomerulus/pathology , Kidney Glomerulus/physiopathology , Kidney Glomerulus/metabolism , Kidney/physiopathology , Kidney/metabolism , Endothelium, Vascular/physiopathology , Endothelium, Vascular/metabolismABSTRACT
Xanthine Oxidoreductase (XOR) is a ubiquitous, essential enzyme responsible for the terminal steps of purine catabolism, ultimately producing uric acid that is eliminated by the kidneys. XOR is also a physiological source of superoxide ion, hydrogen peroxide, and nitric oxide, which can function as second messengers in the activation of various physiological pathways, as well as contribute to the development and the progression of chronic conditions including kidney diseases, which are increasing in prevalence worldwide. XOR activity can promote oxidative distress, endothelial dysfunction, and inflammation through the biological effects of reactive oxygen species; nitric oxide and uric acid are the major products of XOR activity. However, the complex relationship of these reactions in disease settings has long been debated, and the environmental influences and genetics remain largely unknown. In this review, we give an overview of the biochemistry, biology, environmental, and current clinical impact of XOR in the kidney. Finally, we highlight recent genetic studies linking XOR and risk for kidney disease, igniting enthusiasm for future biomarker development and novel therapeutic approaches targeting XOR.