A Role of Intestinal Alkaline Phosphatase 3 (Akp3) in Inorganic Phosphate Homeostasis

Overview

Journal Kidney Blood Press Res

Publisher Karger

Specialty Nephrology

Date 2018 Sep 14

PMID 30212831

Citations 11

Authors

Shohei Sasaki

Hiroko Segawa

Ai Hanazaki

Ruri Kirino

Toru Fujii

Kayo Ikuta

Miwa Noguchi

Sumire Sasaki

Megumi Koike

Kazuya Tanifuji

Yuji Shiozaki

Ichiro Kaneko

Sawako Tatsumi

Takaaki Shimohata

Yoshichika Kawai

Sonoko Narisawa

Jose Luis Millan

Ken-Ichi Miyamoto

Affiliations

Soon will be listed here.

Abstract

Background/aims: Hyperphosphatemia is a serious complication of late-stage chronic kidney disease (CKD). Intestinal inorganic phosphate (Pi) handling plays an important role in Pi homeostasis in CKD. We investigated whether intestinal alkaline phosphatase 3 (Akp3), the enzyme that hydrolyzes dietary Pi compounds, is a target for the treatment of hyperphosphatemia in CKD.

Methods: We investigated Pi homeostasis in Akp3 knockout mice (Akp3-/-). We also studied the progression of renal failure in an Akp3-/- mouse adenine treated renal failure model. Plasma, fecal, and urinary Pi and Ca concentration were measured with commercially available kit, and plasma fibroblast growth factor 23, parathyroid hormone, and 1,25(OH)2D3 concentration were measured with ELISA. Brush border membrane vesicles were prepared from mouse intestine using the Ca2+ precipitation method and used for Pi transport activity and alkaline phosphatase activity. In vivo intestinal Pi absorption was measured with oral 32P administration.

Results: Akp3-/- mice exhibited reduced intestinal type II sodium-dependent Pi transporter (Npt2b) protein levels and Na-dependent Pi co-transport activity. In addition, plasma active vitamin D levels were significantly increased in Akp3-/- mice compared with wild-type animals. In the adenine-induced renal failure model, Akp3 gene deletion suppressed hyperphosphatemia.

Conclusion: The present findings indicate that intestinal Akp3 deletion affects Na+-dependent Pi transport in the small intestine. In the adenine-induced renal failure model, Akp3 is predicted to be a factor contributing to suppression of the plasma Pi concentration.

Citing Articles

Spontaneous Tumor Regression and Reversion: Insights and Associations with Reduced Dietary Phosphate.

Brown R Cancers (Basel). 2024; 16(11).

PMID: 38893245 PMC: 11172109. DOI: 10.3390/cancers16112126.

Involvement of α-klotho in growth hormone (GH) signaling.

Koike M, Sato T, Shiozaki Y, Komiya A, Miura M, Higashi A J Clin Biochem Nutr. 2024; 74(3):221-229.

PMID: 38799134 PMC: 11111466. DOI: 10.3164/jcbn.23-127.

Pediococcus acidilactici reduces tau pathology and ameliorates behavioral deficits in models of neurodegenerative disorders.

Zhang Y, Qian W, Zhang Y, Ma Y, Qian J, Li J Cell Commun Signal. 2024; 22(1):84.

PMID: 38291511 PMC: 10826277. DOI: 10.1186/s12964-023-01419-3.

Ukrainian Consensus on Diagnosis and Management of Vitamin D Deficiency in Adults.

Grygorieva N, Tronko M, Kovalenko V, Komisarenko S, Tatarchuk T, Dedukh N Nutrients. 2024; 16(2).

PMID: 38257163 PMC: 10820145. DOI: 10.3390/nu16020270.

The basics of phosphate metabolism.

Wagner C Nephrol Dial Transplant. 2023; 39(2):190-201.

PMID: 37660247 PMC: 10828206. DOI: 10.1093/ndt/gfad188.

References

Storelli C, Murer H . On the correlation between alkaline phosphatase and phosphate transport in rat renal brush border membrane vesicles. Pflugers Arch. 1980; 384(2):149-53. DOI: 10.1007/BF00584431. View

Brun L, Lombarte M, Roma S, Perez F, Millan J, Rigalli A . Increased calcium uptake and improved trabecular bone properties in intestinal alkaline phosphatase knockout mice. J Bone Miner Metab. 2017; 36(6):661-667. PMC: 6338327. DOI: 10.1007/s00774-017-0887-7. View

Friedlander G, Couette S, Coureau C, Amiel C . Mechanisms whereby extracellular adenosine 3',5'-monophosphate inhibits phosphate transport in cultured opossum kidney cells and in rat kidney. Physiological implication. J Clin Invest. 1992; 90(3):848-58. PMC: 329939. DOI: 10.1172/JCI115960. View

Candeal E, Caldas Y, Guillen N, Levi M, Sorribas V . Intestinal phosphate absorption is mediated by multiple transport systems in rats. Am J Physiol Gastrointest Liver Physiol. 2017; 312(4):G355-G366. DOI: 10.1152/ajpgi.00244.2016. View

Borowitz S, Ghishan F . Maturation of jejunal phosphate transport by rat brush border membrane vesicles. Pediatr Res. 1985; 19(12):1308-12. DOI: 10.1203/00006450-198512000-00021. View

Borowitz S, Ghishan F . Phosphate transport in human jejunal brush-border membrane vesicles. Gastroenterology. 1989; 96(1):4-10. DOI: 10.1016/0016-5085(89)90757-9. View

Inker L, Astor B, Fox C, Isakova T, Lash J, Peralta C . KDOQI US commentary on the 2012 KDIGO clinical practice guideline for the evaluation and management of CKD. Am J Kidney Dis. 2014; 63(5):713-35. DOI: 10.1053/j.ajkd.2014.01.416. View

Ohi A, Hanabusa E, Ueda O, Segawa H, Horiba N, Kaneko I . Inorganic phosphate homeostasis in sodium-dependent phosphate cotransporter Npt2b⁺/⁻ mice. Am J Physiol Renal Physiol. 2011; 301(5):F1105-13. DOI: 10.1152/ajprenal.00663.2010. View

Oshima Y . The phosphatase system in Saccharomyces cerevisiae. Genes Genet Syst. 1998; 72(6):323-34. DOI: 10.1266/ggs.72.323. View

10.

Wagner C, Hernando N, Forster I, Biber J . The SLC34 family of sodium-dependent phosphate transporters. Pflugers Arch. 2013; 466(1):139-53. DOI: 10.1007/s00424-013-1418-6. View

11.

Bilski J, Mazur-Bialy A, Wojcik D, Zahradnik-Bilska J, Brzozowski B, Magierowski M . The Role of Intestinal Alkaline Phosphatase in Inflammatory Disorders of Gastrointestinal Tract. Mediators Inflamm. 2017; 2017:9074601. PMC: 5339520. DOI: 10.1155/2017/9074601. View

12.

De Young M, Scarpa A . Extracellular ATP activates coordinated Na+, Pi, and Ca2+ transport in cardiac myocytes. Am J Physiol. 1991; 260(6 Pt 1):C1182-90. DOI: 10.1152/ajpcell.1991.260.6.C1182. View

13.

Shirazi S, Beechey R, Butterworth P . The use of potent inhibitors of alkaline phosphatase to investigate the role of the enzyme in intestinal transport of inorganic phosphate. Biochem J. 1981; 194(3):803-9. PMC: 1162816. DOI: 10.1042/bj1940803. View

14.

Segawa H, Kaneko I, Takahashi A, Kuwahata M, Ito M, Ohkido I . Growth-related renal type II Na/Pi cotransporter. J Biol Chem. 2002; 277(22):19665-72. DOI: 10.1074/jbc.M200943200. View

15.

Matsuo A, Negoro T, Seo T, Kitao Y, Shindo M, Segawa H . Inhibitory effect of JTP-59557, a new triazole derivative, on intestinal phosphate transport in vitro and in vivo. Eur J Pharmacol. 2005; 517(1-2):111-9. DOI: 10.1016/j.ejphar.2005.05.003. View

16.

Hernando N, Myakala K, Simona F, Knopfel T, Thomas L, Murer H . Intestinal Depletion of NaPi-IIb/Slc34a2 in Mice: Renal and Hormonal Adaptation. J Bone Miner Res. 2015; 30(10):1925-37. DOI: 10.1002/jbmr.2523. View

17.

Radanovic T, Wagner C, Murer H, Biber J . Regulation of intestinal phosphate transport. I. Segmental expression and adaptation to low-P(i) diet of the type IIb Na(+)-P(i) cotransporter in mouse small intestine. Am J Physiol Gastrointest Liver Physiol. 2005; 288(3):G496-500. DOI: 10.1152/ajpgi.00167.2004. View

18.

Zimmermann H . ATP and acetylcholine, equal brethren. Neurochem Int. 2007; 52(4-5):634-48. DOI: 10.1016/j.neuint.2007.09.004. View

19.

Sabbagh Y, Giral H, Caldas Y, Levi M, Schiavi S . Intestinal phosphate transport. Adv Chronic Kidney Dis. 2011; 18(2):85-90. PMC: 3071860. DOI: 10.1053/j.ackd.2010.11.004. View

20.

Kaliannan K, Hamarneh S, Economopoulos K, Nasrin Alam S, Moaven O, Patel P . Intestinal alkaline phosphatase prevents metabolic syndrome in mice. Proc Natl Acad Sci U S A. 2013; 110(17):7003-8. PMC: 3637741. DOI: 10.1073/pnas.1220180110. View