Activity and Expression of Vitamin K-Dependent Gamma-Glutamyl Carboxylase in Patients with Calcium Oxalate Urolithiasis

Abstract

Objectives: To evaluate the correlation between vitamin K-dependent gamma-glutamyl carboxylase (GGCX) and the formation of calcium oxalate urolithiasis (COU). Methods: Renal cortex samples were obtained from patients undergoing nephrectomy and divided into 3 groups: (1) urolithiasic group (n = 44); (2) hydronephrosis-without-stone group (control group A, n = 6), and (3) normal control group (control group B, n = 21). Immunohistochemical technique was established to study the location of GGCX in renal tissues. The carboxylase activity was detected by the isotope-labeled carboxylatic reaction in vitro. We also quantified GGCX mRNA levels using TaqMan real-time reverse-transcription PCR, and protein was detected by Western blot. Results: GGCX was located in the cytoplasm of renal tubular epithelial cells and the activity of GGCX in the urolithiasic group was significantly decreased compared with that of controls (p < 0.05). GGCX mRNA in the urolithiasic group was lower than that in the normal control group, which was on average 7.86-fold underexpressed in the urolithiasic group compared to the normal control group. Protein expression of GGCX in the urolithiasic group (27.64 ± 0.29) was weaker than that in the other 2 control groups (control group A 55.22 ± 0.36, control group B 53.78 ± 0.33), p < 0.05. Conclusions: The activity and expression of GGCX are decreased in renal tissues of patients with COU.

Calcium oxalate monohydrate crystals stimulate monocyte chemoattractant protein-1 and transforming growth factor β1 expression in human renal epithelial cells

“…Physiologically, a high concentration of calcium itself is able to reduce antidiuretic hormone-stimulated water permeability of the collecting duct through the calcium sensing receptor, inducing an increased urinary volume and a reduced risk of supersaturation (3,4). Biochemically, a number of micro-and macromolecular urinary constituents (such as citrate, magnesium and proteins) increase the urinary supersaturation capacity and delay or prevent crystal formation, growth and aggregation (5)(6)(7)(8). At the level of crystal-cell interactions, normal differentiated tubular epithelia have no affinity for crystals, and crystal retention can be prevented by coating crystals with urinary macromolecules (9,10).…”

Carboxylator: incorporating solvent-accessible surface area for identifying protein carboxylation sites

“…The modification is catalyzed by a vitamin K-activated c-glutamyl carboxylase which transforms a glutamate (Glu) residue to a c-carboxyglutamate (Gla) residue upon adding a carbon dioxide (CO 2 ) compound at the c-position [1,2]. Vitamin K-dependent gammaglutamyl carboxylase plays a crucial role in the vitamin K cycle [3] and is associated the formation of calcium oxalate urolithiasis [4]. Carboxylated proteins can be activated when Gla domain binds Ca 2?…”