Noncrystalline uric acid inhibits proteoglycan and glycosaminoglycan synthesis in distal tubular epithelial cells (MDCK) (original) (raw)
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Kidney International, 2005
Background. The interaction between tubular epithelial cells and calcium oxalate crystals or oxalate ions is a very precarious event in the lithogenesis. Urine contains ions, glycoproteins and glycosaminoglycans that inhibit the crystallization process and may protect the kidney against lithogenesis. We examined the effect of oxalate ions and calcium oxalate crystals upon the synthesis of glycosaminoglycans in distal [Madin-Darby canine kidney (MDCK)] and proximal (LLC-PK1) tubular cell lines.
The FASEB Journal, 2019
Recent data suggested a causative role of uric acid (UA) in the development of renal disease, in which endothelial dysfunction is regarded as the key mechanism. Endothelial-to-mesenchymal transition (EndoMT) and shedding of the glycocalyx are early changes of endothelial dysfunction. We investigated whether UA induced EndoMT in HUVECs and an animal model of hyperuricemia fed with 2% oxonic acid for 4 wk. UA induced EndoMT in HUVECs with a generation of reactive oxygen species via the activation of membranous NADPH oxidase (from 15 min) and mitochondria (from 6 h) along with glycocalyx shedding (from 6 h), which were blocked by probenecid. GM6001, an inhibitor of matrix metalloproteinase, alleviated UA-induced glycocalyx shedding and EndoMT. Antioxidants including N-acetyl cysteine, apocynin, and mitotempo ameliorated EndoMT; however, they did not change glycocalyx shedding in HUVECs. In the kidney of hyperuricemic rats, endothelial staining in peritubular capillaries (PTCs) was substantially decreased with a de novo expression of a-smooth muscle actin in PTCs. Plasma level of syndecan-1 was increased in hyperuricemic rats, which was ameliorated by allopurinol. UA caused a phenotypic transition of endothelial cells via induction of oxidative stress with glycocalyx shedding, which could be one of the mechanisms of UA-induced endothelial dysfunction and kidney disease.
Uric acid crystal binding to renal inner medullary collecting duct cells in primary culture
Journal of the American Society of Nephrology : JASN, 1990
Attachment of microcrystals to cellular membranes may be an important component in the pathophysiology of urolithiasis. This study characterizes the concentration-dependent binding of uric acid crystals to rat renal inner medullary collecting duct cells in primary culture. Collecting duct cell cultures grew as monolayers with interspersed aggregates of rounded cells. Cultures were incubated with 14C-uric acid crystals, and the crystals that bound were quantitated by adherent radioactivity. Uric acid crystal adherence demonstrated concentration dependent saturation with a 1/alpha value (maximum micrograms of crystals adhering to 1 cm2 of binding area) of 645 micrograms/cm2. The beta values (fraction of cross-sectional area which bound crystals) of uric acid (mean = 0.15) and calcium oxalate monohydrate (mean = 0.13) crystals did not differ significantly. Uric acid crystal binding was inhibited by pre-bound calcium oxalate monohydrate crystals in a concentration dependent manner. Thes...
Modulation of Proliferating Renal Epithelial Cell Affinity for Calcium Oxalate Monohydrate Crystals
Journal of the American Society of Nephrology, 2004
Adhesion of urinary crystals to distal tubular cells could be a critical event that triggers a cascade of responses ending in kidney stone formation. Monolayer cultures of distal nephronderived MDCKI cells were used as a model to study crystal-cell interactions. COM crystal adhesion reached a peak 2 d after plating and progressively fell thereafter. The decline in crystal binding was accelerated by prostaglandin E 2 (PGE 2) supplementation and delayed by blockade of PG production. Crystals avidly adhered to cells that migrated in to repair a scrape wound made in the monolayer and after a transient hypoglycemic insult. Exposure of MDCKI cells to uric acid crystals and soluble uric acid was also associated with increased crystal adhesion. Treatment of physically or hypoglycemically injured cells with trypsin or neuraminidase reduced crystal binding to baseline levels, suggesting that increased exposure of cell surface glycoproteins mediated the Materials and Methods Cell Culture Renal epithelial cells of the MDCK line, type I, were a gift of Carl
Urinary excretion of glycosaminoglycans in normal and stone forming subjects
Kidney International, 1989
Urinary excretion of glycosaminoglycans in normal and stone forming subjects. There is evidence suggesting that glycosaminoglycans (GAG) are potent inhibitors of growth and aggregation of calcium oxalate crystals in vitro. This finding raises the possibility that the urinary GAG
Natural urinary macromolecular inhibitors: Attenuation of inhibitory activity by urate salts
Kidney International, 1983
Natural urinary macromolecular inhibitors: Attenuation of inhibitory activity by urate salts. The interaction between naturally occurring urinary macromolecular inhibitors of calcium oxalate nucleation and crystal growth and the various urate salts was explored in vitro. The fraction of macromolecules chosen for the study was the one which was previously shown to have a potent inhibitor activity against calcium oxalate nucleation and one which gave a satisfactory yield. As little as 0.025 mg/mI of this fraction (Y-b) was found to inhibit calcium oxalate nucleation by nearly 50% and crystal growth by 31%. Prior incubation of the solution containing Y-b with increasing crystal surface areas (1.1 to 26.2 mm2/ml) of monosodium urate (NaU), monopotassium urate (KU), or uric acid (UA) attenuated the inhibitory action of the Y-b fraction for both nucleation and crystal growth of calcium oxalate. The most prominent effect was elicited by NaU at surface areas as small as 1.1 mm2/ml. Potassium urate and UA were without significant effects until surface areas of 13.1 and 2.6 mm2/ml, respectively, were achieved. These results support an important pathogenetic role for urates (particularly NaU) in the development of hyperuricosuric calcium urolithiasis. L'inhibiteurs des macromolecules urinaires normalement: Attenuation de Ia activité inhibiteur par les sels d'urate. L'interaction entre les inhibiteurs macromoléculaires normalement presents dans l'urine de Ia nuclCation de l'oxalate de calcium et de Ia croissance cristalline et les divers sels d'urate a été explorée in vitro. La fraction de macromolécules choisies pour l'ëtude étaient celle dont il avait ëté montrC auparavant qu'elle était porteuse d'une activilC inhibitrice puissante contre Ia nucleation d'oxalate de calcium ct celle qui donnait un rendement satisfaisant. Une quantité aussi faible que 0,025 mg/mI de cette fraction (Y-b) s'est avérée capable d'inhiber Ia nucleation d'oxalate de calcium d'environ 50% et Ia croissance cristalline de 31%. Une incubation prealable d'une solution contenant Y-b avec des surfaces de cristaux croissantes (1,! a 26,2 mm2/ml) d'urate monosodique (NaU), d'urate monopotassique (KU), ou d'acide urique (UA) a atténué l'action inhibitrice de Ia fraction Y-b sur Ia nucleation et Ia croissance cristalline de l'oxalatc de calcium. L'effet Ic plus marqué était obtenu par du NaU sur des surfaces aussi faibles que 1.1 mm2/ml. L'urate dc potassium et l'UA étaient sans effet significatifjusqu'a des surfaces de 13,1 et 2,6 mm2/ml, respectivement. Ces résultats sont en faveur d'un role physiopathologique important des urates (particulierement de NaU) dans Ic dCveloppement de Ia lithiase urinaire calcique hyperuricosurique.
The Multiple Roles of Urocanic Acid in Health and Disease
Journal of Investigative Dermatology, 2020
Trans-urocanic acid (trans-UCA) is synthesized in the skin, liver, and brain. It is a major natural moisturizing factor in skin and maintains its acid pH. In skin, it isomerizes to cis-UCA following exposure to UVR. Both isomers fulfill multiple roles in health and disease. Cis-UCA has immunomodulatory properties linked with several cutaneous diseases such as skin cancer, atopic dermatitis, and urticaria and associates with systemic diseases including multiple sclerosis. The levels of UCA in the skin, brain, urine, and feces reflect some physiological processes and may be disease biomarkers. Both isomers of UCA have therapeutic potential for a range of disorders.