Abstract
Calcium oxalate (CaOx) kidney stones accumulate within the renal tubule due to high concentrations of insoluble deposits in the urine. Pb2+-induced Ca2+ mobilization along with Pb2+-induced nephrotoxic effects within the proximal tubule have been well established; however, Pb2+ mediated effects within the collecting duct remains insufficiently studied. Thus in vitro and ex vivo model systems were treated with increasing concentrations of lead (II) acetate (PbAc) ± sodium oxalate (Na2C2O4) for 1 hour, both individually and in combination. Pb2+-mediated solution turbidity increased 2 to 5 times greater post- exposure to 75, 100 and 200 μM Pb2+ with the additional co-treatment of 10 mM oxalate in mouse inner medullary collecting duct (mIMCD-3) cells. Additionally, 100 μM and 200 μM Pb2+ alone induced significant levels of intracellular Ca2+ release. To validate Pb2+-mediated effects on the formation of CaOx crystals, alizarin red staining confirmed the presence of CaOx crystallization. Pb2+-induced intracellular Ca2+ was also observed ex vivo in fly Malpighian tubules with significant increases in CaOx crystal formation via Pb2+-induced intracellular Ca2+ release significantly increasing the average crystal number, size, and total area of crystal formation, which was ameliorated by tissue-specific SPoCk C transporter and Capa receptor knockdown. These studies demonstrate Pb2+-induced Ca2+ release likely increases the formation of CaOx crystals, which is modulated by a Gq-linked mechanism with concurrent Ca2+ extracellular mobilization.
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