TY - JOUR A1 - Feger, Martina A1 - Fajol, Abul A1 - Lebedeva, Aleksandra A1 - Meissner, Adrian A1 - Michael, Diana A1 - Völkl, Jakob A1 - Alesutan, Ioana A1 - Schleicher, Erwin A1 - Reichetzeder, Christoph A1 - Hocher, Berthold A1 - Qadri, Syed M. A1 - Lang, Florian T1 - Effect of Carbon Monoxide Donor CORM-2 on Vitamin D-3 Metabolism JF - Kidney & blood pressure research : official organ of the Gesellschaft für Nephrologie N2 - Background/Aims: Carbon monoxide (CO) interferes with cytochrome-dependent cellular functions and acts as gaseous transmitter. CO is released from CO-releasing molecules (CORM) including tricarbonyl-dichlororuthenium (II) dimer (CORM-2), molecules considered for the treatment of several disorders including vascular dysfunction, inflammation, tissue ischemia and organ rejection. Cytochrome P450-sensitive function include formation of 1,25-dihydroxyvitamin D-3 (1,25(OH)(2)D-3) by renal 25-hydroxyvitamin D-3 1-alpha-hydroxylase (Cyp27b1). The enzyme is regulated by PTH, FGF23 and klotho. 1,25(OH)(2)D-3 regulates Ca2+ and phosphate transport as well as klotho expression. The present study explored, whether CORM-2 influences 1,25(OH)(2)D-3 formation and klotho expression. Methods: Mice were treated with intravenous CORM-2 (20 mg/kg body weight). Plasma 1,25(OH)(2)D-3 and FGF23 concentrations were determined by ELISA, phosphate, calcium and creatinine concentrations by colorimetric methods, transcript levels by quantitative RT-PCR and protein expression by western blotting. Fgf23 mRNA transcript levels were further determined in rat osteosarcoma UMR106 cells without or with prior treatment for 24 hours with 20 mu M CORM-2. Results: CORM-2 injection within 24 hours significantly increased FGF23 plasma levels and decreased 1,25(OH)(2)D-3 plasma levels, renal Cyp27b1 gene expression as well as renal klotho protein abundance and transcript levels. Moreover, treatment of UMR106 cells with CORM-2 significantly increased Fgf23 transcript levels. Conclusion: CO-releasing molecule CORM-2 enhances FGF23 expression and release and decreases klotho expression and 1,25(OH)(2)D-3 synthesis. KW - CORM-2 KW - 1,25-Dihydroxyvitamin D-3 KW - Klotho KW - FGF23 KW - Phosphate KW - Calcium Y1 - 2013 U6 - https://doi.org/10.1159/000355730 SN - 1420-4096 SN - 1423-0143 VL - 37 IS - 4-5 SP - 496 EP - 505 PB - Karger CY - Basel ER - TY - GEN A1 - Paßlack, Nadine A1 - Schmiedchen, Bettina A1 - Raila, Jens A1 - Schweigert, Florian J. A1 - Stumpff, Friederike A1 - Kohn, Barbara A1 - Neumann, Konrad A1 - Zentek, Jürgen T1 - Impact of increasing dietary calcium levels on calcium excretion and vitamin D metabolites in the blood of healthy adult cats T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - Background Dietary calcium (Ca) concentrations might affect regulatory pathways within the Ca and vitamin D metabolism and consequently excretory mechanisms. Considering large variations in Ca concentrations of feline diets, the physiological impact on Ca homeostasis has not been evaluated to date. In the present study, diets with increasing concentrations of dicalcium phosphate were offered to ten healthy adult cats (Ca/phosphorus (P): 6.23/6.02, 7.77/7.56, 15.0/12.7, 19.0/17.3, 22.2/19.9, 24.3/21.6 g/kg dry matter). Each feeding period was divided into a 10-day adaptation and an 8-day sampling period in order to collect urine and faeces. On the last day of each feeding period, blood samples were taken. Results Urinary Ca concentrations remained unaffected, but faecal Ca concentrations increased (P < 0.001) with increasing dietary Ca levels. No effect on whole and intact parathyroid hormone levels, fibroblast growth factor 23 and calcitriol concentrations in the blood of the cats were observed. However, the calcitriol precursors 25(OH)D-2 and 25(OH)D-3, which are considered the most useful indicators for the vitamin D status, decreased with higher dietary Ca levels (P = 0.013 and P = 0.033). Increasing dietary levels of dicalcium phosphate revealed an acidifying effect on urinary fasting pH (6.02) and postprandial pH (6.01) (P < 0.001), possibly mediated by an increase of urinary phosphorus (P) concentrations (P < 0.001). Conclusions In conclusion, calcitriol precursors were linearly affected by increasing dietary Ca concentrations. The increase in faecal Ca excretion indicates that Ca homeostasis of cats is mainly regulated in the intestine and not by the kidneys. Long-term studies should investigate the physiological relevance of the acidifying effect observed when feeding diets high in Ca and P. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 542 KW - chronic kidney-disease KW - growth-factor 23 KW - parathyroid-hormone KW - urinary ph KW - phosphorus KW - FGF23 KW - deficiency KW - dogs KW - hypercalciuria KW - secretion Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-411302 SN - 1866-8372 IS - 542 ER - TY - JOUR A1 - Glosse, Philipp A1 - Feger, Martina A1 - Mutig, Kerim A1 - Chen, Hong A1 - Hirche, Frank A1 - Hasan, Ahmed Abdallah Abdalrahman Mohamed A1 - Gaballa, Mohamed Mahmoud Salem Ahmed A1 - Hocher, Berthold A1 - Lang, Florian A1 - Föller, Michael T1 - AMP-activated kinase is a regulator of fibroblast growth factor 23 production JF - Kidney international : official journal of the International Society of Nephrology N2 - Fibroblast growth factor 23 (FGF23) is a proteohormone regulating renal phosphate transport and vitamin D metabolism as well as inducing left heart hypertrophy. FGF23-deficient mice suffer from severe tissue calcification, accelerated aging and a myriad of aging-associated diseases. Bone cells produce FGF23 upon store-operated calcium ion entry (SOCE) through the calcium selective ion channel Orai1. AMP-activated kinase (AMPK) is a powerful energy sensor helping cells survive states of energy deficiency, and AMPK down-regulates Orai1. Here we investigated the role of AMPK in FGF23 production. Fgf23 gene transcription was analyzed by qRT-PCR and SOCE by fluorescence optics in UMR106 osteoblast-like cells while the serum FGF23 concentration and phosphate metabolism were assessed in AMPKa1-knockout and wild-type mice. The AMPK activator, 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) down-regulated, whereas the AMPK inhibitor, dorsomorphin dihydrochloride (compound C) and AMPK gene silencing induced Fgf23 transcription. AICAR decreased membrane abundance of Orai1 and SOCE. SOCE inhibitors lowered Fgf23 gene expression induced by AMPK inhibition. AMPKa1-knockout mice had a higher serum FGF23 concentration compared to wild-type mice. Thus, AMPK participates in the regulation of FGF23 production in vitro and in vivo. The inhibitory effect of AMPK on FGF23 production is at least in part mediated by Orai1-involving SOCE. KW - calcium KW - FGF23 KW - Klotho KW - Orai1 KW - phosphate KW - parathyroid hormone Y1 - 2018 U6 - https://doi.org/10.1016/j.kint.2018.03.006 SN - 0085-2538 SN - 1523-1755 VL - 94 IS - 3 SP - 491 EP - 501 PB - Elsevier CY - New York ER -