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Article: Checkpoint kinase CHk2 controls renal CYp27b1 expression, calcitriol formation, and calcium-phosphate metabolism

TitleCheckpoint kinase CHk2 controls renal CYp27b1 expression, calcitriol formation, and calcium-phosphate metabolism
Authors
KeywordsKlotho
ATM
Calcium/phosphate metabolism
PTH/vit D/FGF23
Issue Date2015
Citation
Pflugers Archiv European Journal of Physiology, 2015, v. 467, n. 9, p. 1871-1880 How to Cite?
Abstract© Springer-Verlag Berlin Heidelberg 2014. Checkpoint kinase 2 (Chk2) is the main effector kinase of ataxia telangiectasia mutated (ATM) and responsible for cell cycle regulation. ATM signaling has been shown to upregulate interferon-regulating factor-1 (IRF-1), a transcription factor also expressed in the kidney. Calcitriol (1,25 (OH)2D3), a major regulator of mineral metabolism, is generated by 25-hydroxyvitamin D 1α-hydroxylase in the kidney. Since 25-hydroxyvitamin D 1α-hydroxylase expression is enhanced by IRF-1, the present study explored the role of Chk2 for calcitriol formation and mineral metabolism. Chk2- deficient mice (chk2−/−) were compared to wild-type mice (chk2+/+). Transcript levels of renal 25-hydroxyvitamin D 1α-hydroxylase, Chk2, and IRF-1 were determined by RTPCR; Klotho expression by Western blotting; bone density by μCT analysis; serum or plasma 1,25 (OH)2D3, PTH, and Cterminal FGF23 concentrations by immunoassays; and serum, fecal, and urinary calcium and phosphate concentrations by photometry. The renal expression of IRF-1 and 25- hydroxyvitamin D 1α-hydroxylase as well as serum 1,25 (OH)2D3 and FGF23 levels were significantly lower in chk2−/− mice compared to chk2+/+ mice. Plasma PTH was not different between the genotypes. Renal calcium and phosphate excretion were significantly higher in chk2−/− mice than in chk2+/+ mice despite hypophosphatemia and normocalcemia. Bone density was not different between the genotypes. We conclude that Chk2 regulates renal 25- hydroxyvitamin D 1α-hydroxylase expression thereby impacting on calcium and phosphate metabolism.
Persistent Identifierhttp://hdl.handle.net/10722/292907
ISSN
2023 Impact Factor: 2.9
2023 SCImago Journal Rankings: 1.361
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorFahkri, Hajar-
dc.contributor.authorZhang, Bingbing-
dc.contributor.authorFajol, Abul-
dc.contributor.authorHernando, Nati-
dc.contributor.authorElvira, Bernat-
dc.contributor.authorMannheim, Julia G.-
dc.contributor.authorPichler, Bernd J.-
dc.contributor.authorDaniel, Christoph-
dc.contributor.authorAmann, Kerstin-
dc.contributor.authorHirao, Atsushi-
dc.contributor.authorHaight, Jillian-
dc.contributor.authorMak, Tak W.-
dc.contributor.authorLang, Florian-
dc.contributor.authorFöller, Michael-
dc.date.accessioned2020-11-17T14:57:28Z-
dc.date.available2020-11-17T14:57:28Z-
dc.date.issued2015-
dc.identifier.citationPflugers Archiv European Journal of Physiology, 2015, v. 467, n. 9, p. 1871-1880-
dc.identifier.issn0031-6768-
dc.identifier.urihttp://hdl.handle.net/10722/292907-
dc.description.abstract© Springer-Verlag Berlin Heidelberg 2014. Checkpoint kinase 2 (Chk2) is the main effector kinase of ataxia telangiectasia mutated (ATM) and responsible for cell cycle regulation. ATM signaling has been shown to upregulate interferon-regulating factor-1 (IRF-1), a transcription factor also expressed in the kidney. Calcitriol (1,25 (OH)2D3), a major regulator of mineral metabolism, is generated by 25-hydroxyvitamin D 1α-hydroxylase in the kidney. Since 25-hydroxyvitamin D 1α-hydroxylase expression is enhanced by IRF-1, the present study explored the role of Chk2 for calcitriol formation and mineral metabolism. Chk2- deficient mice (chk2−/−) were compared to wild-type mice (chk2+/+). Transcript levels of renal 25-hydroxyvitamin D 1α-hydroxylase, Chk2, and IRF-1 were determined by RTPCR; Klotho expression by Western blotting; bone density by μCT analysis; serum or plasma 1,25 (OH)2D3, PTH, and Cterminal FGF23 concentrations by immunoassays; and serum, fecal, and urinary calcium and phosphate concentrations by photometry. The renal expression of IRF-1 and 25- hydroxyvitamin D 1α-hydroxylase as well as serum 1,25 (OH)2D3 and FGF23 levels were significantly lower in chk2−/− mice compared to chk2+/+ mice. Plasma PTH was not different between the genotypes. Renal calcium and phosphate excretion were significantly higher in chk2−/− mice than in chk2+/+ mice despite hypophosphatemia and normocalcemia. Bone density was not different between the genotypes. We conclude that Chk2 regulates renal 25- hydroxyvitamin D 1α-hydroxylase expression thereby impacting on calcium and phosphate metabolism.-
dc.languageeng-
dc.relation.ispartofPflugers Archiv European Journal of Physiology-
dc.subjectKlotho-
dc.subjectATM-
dc.subjectCalcium/phosphate metabolism-
dc.subjectPTH/vit D/FGF23-
dc.titleCheckpoint kinase CHk2 controls renal CYp27b1 expression, calcitriol formation, and calcium-phosphate metabolism-
dc.typeArticle-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1007/s00424-014-1625-9-
dc.identifier.pmid25319519-
dc.identifier.scopuseid_2-s2.0-84943357065-
dc.identifier.volume467-
dc.identifier.issue9-
dc.identifier.spage1871-
dc.identifier.epage1880-
dc.identifier.eissn1432-2013-
dc.identifier.isiWOS:000359812600002-
dc.identifier.issnl0031-6768-

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