The purpose of this core is to provide support for studies on epithelial Ca 2+ channels (ECaC) and the electrogenic sodium/dicarboxylate co-transporter (NaDC-1) in components I, III, and IV. ECaC channels are present in the apical membrane of intestine and the distal convoluted tubule (DCT) of kidney and serve as gatekeepers for transcellular Ca 2+ transport in these sites. ECaC is a major target for many hormones that regulate gastrointestinal and kidney Ca 2+ absorption, such as parathyroid hormone, vitamin D, etc (1). cDNAs for ECaC and its isoforms have recently been isolated by Dr. Bindels' (2) and Dr. Hediger's groups (3, 4) independently. We have also isolated cDNA for rabbit ECaC1 and obtained cDNA for mouse ECaC2 from Dr. Bindels (consultant for this core) NaDC-1 in the proximal tubules reabsorbs filtered Krebs cycle intermediates and plays an important role in the regulation of urinary citrate concentrations (5). Low urinary citrate is an important risk factor for formation of kidney stone. In component I, we will test the hypothesis that protein product of an absorptive hypercalciuria (AH)-related gene, AH-related adenylate cyclase (AHRAC), regulates ECaC channel activity. In component III project 1, we will investigate the role of intracellular vs extracellular pH in the regulation of the electrogenic NaDC-1 (6). In component III project 2, we will test the hypothesis that acid inhibition of ECaCl-mediated Ca 2+ reabsorption in DCT contributes to the hypercalciuria induced by a high dietary protein intake and the hypothesis that membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2) regulates ECaC1 channel activity. In component IV, we will test the hypothesis that down-regulation of calbindin-D28k by estrogen lack (in addition to the downregulation of ECaC) is important for renal calcium. leak and examine the molecular mechanism by which calbindin- D28k regulates Ca 2+ reabsorption through ECaC.
| Xu, Li Hao Richie; Maalouf, Naim M (2017) Effect of acute hyperinsulinemia on magnesium homeostasis in humans. Diabetes Metab Res Rev 33: |
| Xu, Li Hao Richie; Adams-Huet, Beverley; Poindexter, John R et al. (2017) Temporal Changes in Kidney Stone Composition and in Risk Factors Predisposing to Stone Formation. J Urol 197:1465-1471 |
| Sakhaee, Khashayar; Poindexter, John; Aguirre, Crystal (2016) The effects of bariatric surgery on bone and nephrolithiasis. Bone 84:1-8 |
| Hu, Ming Chang; Shi, Mingjun; Cho, Han Jun et al. (2015) Klotho and phosphate are modulators of pathologic uremic cardiac remodeling. J Am Soc Nephrol 26:1290-302 |
| Hajibeigi, Asghar; Dioum, Elhadji M; Guo, Jianfei et al. (2015) Identification of novel regulatory NFAT and TFII-I binding elements in the calbindin-D28k promoter in response to serum deprivation. Biochem Biophys Res Commun 465:414-420 |
| Yoon, Vivienne; Adams-Huet, Beverley; Sakhaee, Khashayar et al. (2013) Hyperinsulinemia and urinary calcium excretion in calcium stone formers with idiopathic hypercalciuria. J Clin Endocrinol Metab 98:2589-94 |
| Capolongo, Giovanna; Abul-Ezz, Sameh; Moe, Orson W et al. (2012) Subclinical celiac disease and crystal-induced kidney disease following kidney transplant. Am J Kidney Dis 60:662-7 |
| Cameron, MaryAnn; Maalouf, Naim M; Poindexter, John et al. (2012) The diurnal variation in urine acidification differs between normal individuals and uric acid stone formers. Kidney Int 81:1123-30 |
| Sakhaee, Khashayar; Capolongo, Giovanna; Maalouf, Naim M et al. (2012) Metabolic syndrome and the risk of calcium stones. Nephrol Dial Transplant 27:3201-9 |
| Nguyen, Trang Q; Maalouf, Naim M; Sakhaee, Khashayar et al. (2011) Comparison of insulin action on glucose versus potassium uptake in humans. Clin J Am Soc Nephrol 6:1533-9 |
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