Kidney Week

Abstract: SA-PO1064

Reduced Secretion of PTH and Hypocalcemia in Systemic Heterozygous ATP2B1 Null Mice

Session Information

• Na+, K+, Cl-
  November 04, 2017 | Location: Hall H, Morial Convention Center
  Abstract Time: 10:00 AM - 10:00 AM

Category: Fluid, Electrolytes, and Acid-Base

• 703 Na+, K+, Cl- Basic

Authors

• Ehara, Yosuke, Yokohama City University Graduate School of Medicine, Yokohama-shi, Kanagawa, Japan

Yosuke Ehara,

• Hirawa, Nobuhito, Yokohama City University Medical Center, Yokohama, Japan

Nobuhito Hirawa,

• Fujiwara, Akira, Yokohama City University Medical Center, Yokohama, Japan

Akira Fujiwara,

• Tamura, Kouichi, Yokohama City University Graduate School of Medicine, Yokohama-shi, Kanagawa, Japan

Kouichi Tamura,

Background

We reported the association between high blood pressure and ATP2B1 gene in Japanese population through Millennium Genome Project. ATP2B1 is a gene encoding plasma membrane calcium ATPase 1 (PMCA1), which is known to be expressed throughout the body. PMCA1 plays a role of discharging Ca ions from the inside of the cell to the outside of the cell, and strictly adjusts the intracellular Ca concentration. In subsequent studies we reported that systemic heterozygous ATP2B1 deficient mice exhibited hypertension and reduced eNOS activity, NO production was involved. In addition, it was confirmed that the mouse exhibited hypocalcemia. Therefore, in order to investigate the mechanism of hypocalcemia, we studied bone, small intestine, kidney and parathyroid gland, which are important organs related to Ca metabolism.

Methods

Blood test, urinalysis, bone formation , bone resorption marker, bone density, bone tissue, and the expression levels of Ca regulatory protein in the small intestine in the Systemic heterozygous ATP2B1 deficient mice (ATP2B1^+/-) and the control mice (ATP2B1^+/+) were compared.

Results

In the ATP2B1^+/- mice, bone mineral density (ATP2B1^+/- versus ATP2B1^+/+ : 689.0 ± 12.9 versus 645.2 ±9.2 ; P<0.05), bone mass and urinary calcium excretion (0.769 ± 0.117 versus 0.330 ± 0.082 ; P<0.05) were increased, serum intact PTH (153.6 ± 41.0 versus 324.4 ± 41.4 ; P<0.05) and ATP2B1 expression of intestine (0.56 ± 0.092 versus 1.00 ± 0.117 ; P<0.05) were decreased, compared with control mice. In the intestine, no significant change was observed in the expression levels of various Ca regulatory proteins other than ATP2B1.

Conclusion

Systemic heterozygous ATP2B1 deficient mice exhibited hypocalcemia, and increased bone density and decreased PTH secretion. ATP2B1 might play important roles in bone metabolism.