The goal of this project is investigate pathophysiological basis of high protein intake-induced hypercalciuria. Epithelial Ca 2+ channels (ECaC1) are present in the apical membrane of the distal convoluted tubule (DCT) of kidney and play an important role in the maintenance of overall calcium homeostasis. Our preliminary results indicate that hypercalciuria associated with a high protein intake is, at least partly, caused by acid inhibition of ECaC1-mediated Ca 2+ reabsorption in DCT.
In Specific Aim 1, we will examine the molecular mechanism of acid inhibition of ECaC1. Likely candidates of """"""""pH sensor"""""""" for acid regulation of ECaC1 will be mutated by site-directed mutagenesis. The activity of wild type and mutant channels will be examined by whole-cell patch-clamp recording. Membrane phospholipid, phosphatidylinositol 4,5-bisphosphate (PIP2) has recently emerged as a unique regulator of channel function.
In Specific Aim 2, we will examine the hypothesis that PIP2 regulation of ECaC1 channel underlines the mechanism by which prostaglandin E2 worsens the high protein intake-induced hypercalciuria.
In Specific Aim 3, we will confirm that luminal acidification inhibits Ca 2+ reabsorption in the distal convoluted tubules (DCT). In vivo microperfusion of rat DCT will be performed to examine the effect of luminal pH on Ca 2+ reabsorption. These studies will help understand the mechanism of hypercalciuria, not only during high dietary protein intake but also under conditions of chronic metabolic acidosis.
| 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 |
| Sakhaee, Khashayar; Capolongo, Giovanna; Maalouf, Naim M et al. (2012) Metabolic syndrome and the risk of calcium stones. Nephrol Dial Transplant 27:3201-9 |
| 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 |
| 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 |
Showing the most recent 10 out of 226 publications
