Calcitonin induces 25-hydroxyvitamin D3 1α-hydroxylase mRNA expression via protein kinase C pathway in LLC-PK1 cells

Noriko Yoshida, Tadashi Yoshida, Akira Nakamura, Toshiaki Monkawa, Matsuhiko Hayashi, Takao Saruta

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

The biosynthesis of 1α, 25-dihydroxyvitamin D3 from 25-hydroxyvitamin D3 is catalyzed by 25-hydroxyvitamin D3 1α-hydroxylase (CYP27B1) in renal proximal tubules. It was recently demonstrated that LLC-PK1 cells express CYP27B1 mRNA, which is regulated by intracellular cAMP but not vitamin D3. To clarify the effect of calcitonin on vitamin D3 metabolism in vitro, LLC- PK1 cells were incubated with hormonal factors, and expression of CYP27B1 mRNA was measured by quantitative reverse transcription-PCR. Calcitonin at 100 nmol/L significantly increased CYP27B1 mRNA expression by 24 h (271 ± 21% of control). Incubation with calcitonin over a range of 1 μmol/L to 1 pmol/L resulted in a concentration-dependent increase in CYP27B1 mRNA levels. It is known that the calcitonin receptor has dual intracellular signaling pathways, via protein kinases A and C. Both 500 μmol/L 8-bromo-cAMP, a protein kinase A activator, and 100 nmol/L phorbol 12-myristate 3-acetate, a protein kinase C activator, increased CYP27B1 mRNA levels at 24 h (207 ± 54 and 246 ± 58% of control, respectively). However, calcitonin-induced CYP27B1 mRNA expression was only inhibited by the protein kinase C inhibitors staurosporine and calphostin C. The protein kinase A inhibitors Rp-cAMPS at 10 and 100 μmol/L and H-89 at 10 μmol/L had no effect on the action of calcitonin, in spite of cAMP-activation by calcitonin. The present data suggest that calcitol in upregulates CYP25B1 mRNA expression via the protein kinase C pathway in LLC-PK1 cells.

Original languageEnglish
Pages (from-to)2474-2479
Number of pages6
JournalJournal of the American Society of Nephrology
Volume10
Issue number12
Publication statusPublished - 1999 Dec 1

ASJC Scopus subject areas

  • Nephrology

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