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1.
A number of recent clinical observations suggest that vitamin D3plays an important role in maintaining normal cardiovascular function, either directly through its receptor in cardiac muscle, or indirectly through its infuence on circulating levels of calcium or on other regulatory factors. By using an antibody directed against the recombinant vitamin D3receptor, we have identified the receptor protein for 1,25(OH)2D3in tissue from two human hearts. The identification of the 1,25(OH)2D3receptor in human heart lends credence to the hypothesis that 1,25(OH)2D3directly effects the human heart and may be involved in several clinically relevant pathological conditions involving the vitamin D3endocrine system. 相似文献
2.
Aims
Epidemiological and interventional studies have suggested a protective role for vitamin D in cardiovascular disease, and basic research has implicated vitamin D as a potential inhibitor of fibrosis in a number of organ systems; yet little is known regarding direct effects of vitamin D on human cardiac cells. Given the critical role of fibrotic responses in end stage cardiac disease, we examined the effect of active vitamin D treatment on fibrotic responses in primary human adult ventricular cardiac fibroblasts (HCF-av), and investigated the relationship between circulating vitamin D (25(OH)D3) and cardiac fibrosis in human myocardial samples.Methods and Results
Interstitial cardiac fibrosis in end stage HF was evaluated by image analysis of picrosirius red stained myocardial sections. Serum 25(OH)D3 levels were assayed using mass spectrometry. Commercially available HCF-av were treated with transforming growth factor (TGF)β1 to induce activation, in the presence or absence of active vitamin D (1,25(OH)2D3). Functional responses of fibroblasts were analyzed by in vitro collagen gel contraction assay. 1,25(OH)2D3 treatment significantly inhibited TGFβ1-mediated cell contraction, and confocal imaging demonstrated reduced stress fiber formation in the presence of 1,25(OH)2D3. Treatment with 1,25(OH)2D3 reduced alpha-smooth muscle actin expression to control levels and inhibited SMAD2 phosphorylation.Conclusions
Our results demonstrate that active vitamin D can prevent TGFβ1-mediated biochemical and functional pro-fibrotic changes in human primary cardiac fibroblasts. An inverse relationship between vitamin D status and cardiac fibrosis in end stage heart failure was observed. Collectively, our data support an inhibitory role for vitamin D in cardiac fibrosis. 相似文献3.
C.J. Laing D.R. Fraser 《Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology》1999,123(4):389
The apparent plasma concentration of vitamin D binding protein (DBP) in an iguanian lizard, Pogona barbata, and the affinity of this protein for 25-hydroxyvitamin D3 (25(OH)D3), 25-hydroxyvitamin D2 (25(OH)D2), and 1,25-dihydroxyvitamin D3 (1,25(OH)D3) was found to resemble more closely that of the domestic hen than that of the human. The characteristics of Pogona DBP, the pattern of vitamin D metabolites derived from injected radioactive vitamin D3 and the plasma concentrations of endogenous 25-hydroxyvitamin D (25(OH)D) in a range of iguanian lizards have been examined. The findings suggest that 25-hydroxyvitamin D (25(OH)D) is the major metabolite of vitamin D, and that it may represent the storage form of vitamin D in these species in the same way as in mammals. High concentrations of vitamin D within iguanian embryos and egg yolks suggest a role for this compound in embryogenesis in these species, and perhaps indicates that there is a mechanism for vitamin D delivery to eggs comparable to that found in the domestic chicken. 相似文献
4.
5.
The active form of vitamin D, 1alpha, 25-dihydroxyvitamin D3 (1,25(OH)2D3), mediates both genomic and rapid non-genomic actions in heart cells. We have previously shown that the vitamin D receptor (VDR) is located in the t-tubular structure of cardiomyocytes. Here we show that VDR specifically interacts with Caveolin-3 in the t-tubules and sarcolemma of adult rat cardiac myocytes. Co-immunoprecipitation studies using VDR antibodies revealed that Caveolin-3 specifically co-precipitates with the VDR and similarly the VDR is co-precipitated with Caveolin-3 antibody. Confocal immuno-fluorescence microscopy analysis also showed co-localization of VDR and Caveolin-3 in t-tubules and sarcolemma. The non-genomic effects of the functional VDR were studied in electrically stimulated myocytes isolated from adult rat hearts. Sarcomere shortening and re-lengthening were measured in 1,25(OH)2D3 treated cardiac myocytes. A 1 nM treatment decreased peak shortening within minutes, suggesting a rapid effect through the membrane-bound VDR. This novel finding of the interaction between VDR and Caveolin-3 is fundamentally important in understanding 1,25(OH)2D3 signal transduction in heart cells and provides further evidence that VDR plays a role in regulation of heart structure and function. 相似文献
6.
Aim was to elucidate autonomic responses to dynamic and static (isometric) exercise of the lower limbs eliciting the same moderate heart rate (HR) response. Method: 23 males performed two kinds of voluntary exercise in a supine position at similar heart rates: static exercise (SE) of the lower limbs (static leg press) and dynamic exercise (DE) of the lower limbs (cycling). Subjective effort, systolic (SBP) and diastolic blood pressure (DBP), mean arterial pressure (MAP), rate pressure product (RPP) and the time between consecutive heart beats (RR-intervals) were measured. Time-domain (SDNN, RMSSD), frequency-domain (power in the low and high frequency band (LFP, HFP)) and geometric measures (SD1, SD2) as well as non-linear measures of regularity (approximate entropy (ApEn), sample entropy (SampEn) and correlation dimension D2) were calculated. Results: Although HR was similar during both exercise conditions (88±10 bpm), subjective effort, SBP, DBP, MAP and RPP were significantly enhanced during SE. HRV indicators representing overall variability (SDNN, SD 2) and vagal modulated variability (RMSSD, HFP, SD 1) were increased. LFP, thought to be modulated by both autonomic branches, tended to be higher during SE. ApEn and SampEn were decreased whereas D2 was enhanced during SE. It can be concluded that autonomic control processes during SE and DE were qualitatively different despite similar heart rate levels. The differences were reflected by blood pressure and HRV indices. HRV-measures indicated a stronger vagal cardiac activity during SE, while blood pressure response indicated a stronger sympathetic efferent activity to the vessels. The elevated vagal cardiac activity during SE might be a response mechanism, compensating a possible co-activation of sympathetic cardiac efferents, as HR and LF/HF was similar and LFP tended to be higher. However, this conclusion must be drawn cautiously as there is no HRV-marker reflecting “pure” sympathetic cardiac activity. 相似文献
7.
Tachi K Takami M Zhao B Mochizuki A Yamada A Miyamoto Y Inoue T Baba K Kamijo R 《Cell and tissue research》2010,342(2):213-220
1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] induces osteoclast formation via induction of receptor activator of NF-κB ligand (RANKL, also called TNF-related activation-induced cytokine: TRANCE) in osteoblasts. In cocultures of mouse bone marrow cells and osteoblasts, 1,25(OH)2D3 induced osteoclast formation in a dose-dependent manner, with maximum osteoclast formation observed at concentrations greater than 10?9 M of 1,25(OH)2D3. In the presence of bone morphogenetic protein 2 (BMP-2), the maximum formation of osteoclasts was seen with lower concentrations of 1,25(OH)2D3 (greater than 10?11 M), suggesting that BMP-2 enhances osteoclast formation induced by 1,25(OH)2D3. In addition, the expressions of RANKL mRNA and proteins were induced by 1,25(OH)2D3 in osteoblasts, and further upregulated by BMP-2. In mouse bone marrow cell cultures without 1,25(OH)2D3, BMP-2 did not enhance osteoclast differentiation induced by recombinant RANKL and macrophage colony-stimulating factor (M-CSF), indicating that BMP-2 does not target osteoclast precursors. Furthermore, BMP-2 up-regulated the expression level of vitamin D receptor (VDR) in osteoblasts. These results suggest that BMP-2 regulates mouse osteoclast differentiation via upregulation of RANKL in osteoblasts induced by 1,25(OH)2D3. 相似文献
8.
Cytosol prepared from small intestine of vitamin D-sufficient rabbits contains a specific high-affinity binding protein for 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). This binding protein sediments at 3.0–3.5 S in sucrose density gradients containing 0.3 m KCl. Scatchard analysis using intestinal cytosol demonstrated a Kd of 0.05 nm and a maximum binding capacity of 92 fmol/mg cytosol protein for 1,25(OH)2D3 at 4°C. Competitive binding studies with various metabolites of vitamin D showed a relative binding affinity of this protein for 1,25(OH)2D3 > 25-hydroxy-vitamin D3 > vitamin D3. With 200 μg of rabbit intestinal cytosol protein, as little as 1.0–2.5 pg of 1,25(OH)2D3 reproducibly displaced the tracer sterol from the binding protein. Analyses of human plasma 1,25(OH)2D3 content yielded values consistent with published results. The vitamin D-replete rabbit provides a convenient, plentiful, and inexpensive source of binding protein for 1,25(OH)2D3 assays. 相似文献
9.
Yunzi Chen Juan Kong Tao Sun George Li Frances L. Szeto Weicheng Liu Dilip K. Deb Youli Wang Qun Zhao Ravi Thadhani Yan Chun Li 《Archives of biochemistry and biophysics》2011,(2):72
Plasminogen activator inhibitor (PAI)-1 is a major fibrinolytic inhibitor. High PAI-1 is associated with increased renal and cardiovascular disease risk. Previous studies demonstrated PAI-1 down-regulation by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), but the molecular mechanism remains unknown. Here we show that exposure of mouse embryonic fibroblasts to TNFα or LPS led to a marked induction of PAI-1, which was blunted by 1,25(OH)2D3, NF-κB inhibitor or p65 siRNA, suggesting the involvement of NF-κB in 1,25(OH)2D3-induced repression. In mouse Pai-1 promoter a putative cis-κB element was identified at −299. EMSA and ChIP assays showed that TNF-α increased p50/p65 binding to this κB site, which was disrupted by 1,25(OH)2D3. Luciferase reporter assays showed that PAI-1 promoter activity was induced by TNFα or LPS, and the induction was blocked by 1,25(OH)2D3. Mutation of the κB site blunted TNFα, LPS or 1,25(OH)2D3 effects. 1,25(OH)2D3 blocked IκBα degradation and arrested p50/p65 nuclear translocation. In mice LPS stimulated PAI-1 expression in the heart and macrophages, and the stimulation was blunted by pre-treatment with a vitamin D analog. Together these data demonstrate that 1,25(OH)2D3 down-regulates PAI-1 by blocking NF-κB activation. Inhibition of PAI-1 production may contribute to the reno- and cardio-protective effects of vitamin D. 相似文献
10.
A reexamination of the equilibrium and the kinetics of 1,25-dihydroxy vitamin D3 binding with its receptor in chick intestinal cytosol was performed because of the recent availability in our laboratory of high specific activity 1,25-dihydroxy[]vitamin D3 (160 Ci/mmol). Under saturating conditions at 25 °C, Scatchard analysis revealed an equilibrium dissociation constant (Kd) of 7.1 × 10?11m which is several fold lower than previously reported for this binding reaction. Furthermore, an estimate of 1.8 × 103 receptor sites per cell was obtained from the intercept of the line with the abscissa of the Scatchard plot. From a kinetic analysis of 1,25-dihydroxy vitamin D3 binding with chick intestinal cytosol, association and dissociation rate constants were determined. Values that were obtained at 25 °C for these processes were 9.5 × 108m? min? and 7.1 × 10?3 min?, respectively. Although these studies, such as for other steroid hormones, were carried out using a crude native cytosol preparation, we have been able to demonstrate unequivocally through the use of high specific activity 1,25-dihydroxy[] vitamin D3 a truly high affinity binding site. 相似文献
11.
W. E. Stumpf M. Sar F. A. Reid S. Huang R. Narbaitz H. F. DeLuca 《Cell and tissue research》1981,221(2):333-338
Summary After injection of radiolabeled 1,25 (OH)2 vitamin D3, nuclear concentration of radioactivity is observed in parenchymal cells of the parathyroid gland in pregnant, adult male, and 10-day male neonatal rats. In competition studies with unlabeled 1,25 (OH)2 vitamin D3, but not with 25 (OH) vitamin D3, nuclear uptake is prevented. Experiments with 3H 25 (OH) vitamin D3, in contrast to 3H 1,25 (OH)2 vitamin D3, do not show nuclear concentration in cells of the parathyroid. The results of the autoradiographic studies suggest the presence of receptors for a direct effect of 1,25 (OH)2 vitamin D3 on the parathyroid gland for modulation of parathyroid hormone secretion. 相似文献
12.
Ramesh K. Wali Marc Bissonnette Kenneth Jiang Sharon M. Niedziela Sharad Khare Hemant K. Roy Michael D. Sitrin Thomas A. Brasitus 《Journal of cellular physiology》1995,162(2):172-180
Our laboratory has recently demonstrated that 1,25-dihydroxyvitamin D3(1,25(OH)2D3) rapidly stimulated membrane polyphosphoinositide breakdown and increased intracellular calcium, as well as activated protein kinase C (PKC) in vitamin D-sufficient rat colonocytes. These effects of 1,25(OH)2D3 were, however, lost in vitamin D-insufficient rats and restored by the in vivo repletion of 1,25(OH)2D3. In the present studies we have examined the ability of 1,25(OH)2D3 to stimulate the phosphorylation of colonic membrane proteins in intact D-sufficient cells. In addition, we investigated the effects of vitamin D status on the phosphorylation of these membrane proteins in broken cell preparations. These studies demonstrated that 1,25(OH)2D3 increased the phosphorylation of at least two colonic membrane proteins with apparent molecular weights of 42,000 (pp42) and 48,000 (pp48) in intact cells of vitamin D-sufficient rats. Moreover, in vitamin D-sufficient rats, treatment of colonocytes with 1,25(OH)2D3 or 12-Otertradecanoyl phorbol 13-acetate (TPA), a known activator of PKC, significantly increased the phosphorylation of pp42 and pp48 in broken cell preparations. The kinetics of these phosphorylations in response to 1,25(OH)2D3 were both rapid and transient. In addition, PKC19–36, a specific PKC inhibitor, decreased the phosphorylation of pp42 and pp48, whereas okadaic acid (OA), a type 1 and 2A protein phosphatase inhibitor, further augmented their phosphorylation in response to 1,25(OH)2D3. The isoelectric points of pp42 and pp48 were 5.79 and 5.97, respectively, and both were predominantly phosphorylated on threonine residues. In contrast to our findings in colonocytes from vitamin D-sufficient animals, basal phosphorylation of pp42 and pp48 were increased in membranes prepared from vitamin D-insufficient rats. Moreover, these phosphorylations failed to change in response to 1,25(OH)2D3-treatment of colonocytes from vitamin D-insufficient rats. The basal phosphorylation of each of these proteins was restored to control levels, as was their ability to respond to the direct addition of 1,25(OH)2D3 following the in vivo repletion of vitamin D-insufficient rats with this secosteroid. In summary, we have identified two acidic membrane proteins from rat colonocytes that are phosphorylated in both intact and broken cell preparations in response to 1,25(OH)2D3 treatment, an event modulated by vitamin D status and mediated, at least in part, by PKC. © 1995 Wiley-Liss, Inc. 相似文献
13.
Specific binding proteins for 1,25-dihydroxyvitamin D3 were identified in bovine mammary tissue obtained from lactating and non-lactating mammary glands by sucrose density gradient centrifugation. The macromolecules had characteristic sedimentation coefficients of 3.5-3.7 S. The interaction of l,25-dihydroxy[3H]vitamin D3 with the macromolecule of the mammary gland cytosol occurred at low concentrations, was saturable, and was a high affinity interaction (Kd = 4.2 × 10?10M at 25 °C). Binding was reversed by excess unlabeled 1,25-dihydroxyvitamin D3, was destroyed by heat and/or incubation with trypsin. It is thus inferred that this macromolecule is protein as it is not destroyed by ribonuclease or deoxyribonuclease. 25-hydroxyvitamin D3, 24,25-dihydroxyvitamin D3, and vitamin D3 did not effectively compete with 1,25-dihydroxyvitamin D3 for binding to cytosol of mammary tissue at near physiological concentrations of these analogs, thus demonstrating the specificity of the binding protein for 1,25-dihydroxyvitamin D3. In vitro subcellular distribution of 1,25-dihydroxy[3H]vitamin D3 demonstrated a time- and temperature-dependent movement of the hormone from the cytoplasm to the nucleus. By 90 min at 25 °C 72% of the 1,25-dihydroxy[3H]vitamin D3 was associated with the nucleus. In addition a 5–6 S macromolecule which binds 25-hydroxy[3H]vitamin D3 was demonstrated in mammary tissue. Finally, it is possible that the receptor-hormone complex present in mammary tissue may function in a manner analogous to intestinal tissue, resulting in the control of calcium transport by 1,25-dihydroxyvitamin D3 in this tissue. 相似文献
14.
Background
Vitamin D3, the most physiologically relevant form of vitamin D, is an essential organic compound that has been shown to have a crucial effect on the immune responses. Vitamin D3 ameliorates the onset of the experimental autoimmune encephalomyelitis (EAE); however, the direct effect of vitamin D3 on T cells is largely unknown.Methodology/Principal Findings
In an in vitro system using cells from mice, the active form of vitamin D3 (1,25-dihydroxyvitamin D3) suppresses both interleukin (IL)-17-producing T cells (TH17) and regulatory T cells (Treg) differentiation via a vitamin D receptor signal. The ability of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) to reduce the amount of IL-2 regulates the generation of Treg cells, but not TH17 cells. Under TH17-polarizing conditions, 1,25(OH)2D3 helps to increase the numbers of IL-10-producing T cells, but 1,25(OH)2D3''s negative regulation of TH17 development is still defined in the IL-10−/− T cells. Although the STAT1 signal reciprocally affects the secretion of IL-10 and IL-17, 1,25(OH)2D3 inhibits IL-17 production in STAT1−/− T cells. Most interestingly, 1,25(OH)2D3 negatively regulates CCR6 expression which might be essential for TH17 cells to enter the central nervous system and initiate EAE.Conclusions/Significance
Our present results in an experimental murine model suggest that 1,25(OH)2D3 can directly regulate T cell differentiation and could be applied in preventive and therapeutic strategies for TH17-mediated autoimmune diseases. 相似文献15.
H E Paaren M A Fivizzani H K Schnoes H F De Luca 《Archives of biochemistry and biophysics》1981,209(2):579-583
1α,25-Difluorovitamin D3 has been synthesized by reacting 1,25-dihydroxyvitamin D3-3-acetate with diethylaminosulfurtrifluoride followed by hydrolysis. Retention of configuration of the fluoro group in this reaction was demonstrated by physical studies using 1α-fluoro and 1β-fluorovitamin D3 models. The 1,25-difluorovitamin D3 compound possessed no vitamin D-like activity demonstrating the importance of 1α- and 25-hydroxylations of vitamin D for activity. However, 1,25-difluorovitamin D3 had no anti-25-hydroxylation activity and no antivitamin D activity. Since 25-fluorovitamin D3 has anti-25-hydroxylase activity, it appears the introduction of a fluoro group on the 1 position diminishes interaction of the vitamin D molecule with the 25-hydroxylase system. 相似文献
16.
Nuclear receptors for 1,25(OH)2 vitamin D3 in thymus reticular cells studied by autoradiography 总被引:1,自引:0,他引:1
Summary After injection of 3H 1,25(OH)2 vitamin D3 to rats fed a vitamin D-deficient diet, nuclear concentration and retention of radioactivity exists in reticular cells of the thymus medulla and cortex, as well as outer cells of developing Hassal's corpuscles. Lymphocytes do not show nuclear concentration of radioactivity. Nuclear concentration in reticular cells is prevented by prior injection of excess 1,25(OH)2 vitamin D3. The results indicate that reticular-endothelial cells contain nuclear receptors for 1,25(OH)2 vitamin D3 and suggest that effects of 1,25(OH)2 vitamin D3 on immune response and lymphocyte differentiation are indirect and mediated through genomic modulation of reticular cell functions such as messenger secretion. 相似文献
17.
Adrian Sturza Ioana Pavel Sebastian Ancușa Corina Danciu Cristina Dehelean Oana Duicu Danina Muntean 《Molecular and cellular biochemistry》2018,444(1-2):103-108
This study examined the hypothesis that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) upregulates the insulin-independent signaling cascade of glucose metabolism. C2C12 myotubes were treated with high glucose (HG, 25 mM) and 1,25(OH)2D3 (0–50 nM). 1,25(OH)2D3 supplementation upregulated both insulin-independent (SIRT1) and insulin-dependent (p-IRS) signaling molecules, and stimulated the GLUT4 translocation, and glucose uptake in HG-treated myotubes. The effect of 1,25(OH)2D3 on IRS1 phosphorylation, GLUT4 translocation, and glucose uptake was attenuated in SIRT1-knockdown myotubes. Treatment with 1,25(OH)2D3, coupled with insulin, enhanced GLUT4 translocation and glucose uptake compared to treatment with either insulin or 1,25(OH)2D3 alone in HG-treated myotubes, which suggests that insulin-independent signaling molecules can contribute to the higher glucose metabolism observed in 1,25(OH)2D3 and insulin-treated cells. The data, therefore, suggest that 1,25(OH)2D3 increases glucose consumption by inducing SIRT1 activation, which in turn increases IRS1 phosphorylation and GLUT4 translocation in myotubes. 相似文献
18.
Barbara E. Kream Robert D. Reynolds Joyce C. Knutson John A. Eisman Hector F. DeLuca 《Archives of biochemistry and biophysics》1976,176(2):779-787
The binding of 25-hydroxy-[26,27-3H]vitamin D3 and 1,25-dihydroxy-[26,27-3H]vitamin D3 to the cytosol of intestinal mucosa of chicks and rats has been studied by sucrose gradient analysis. The cytosol from chick mucosa showed variable binding of 1,25-dihydroxyvitamin D3 to a 3.0S macromolecule which has high affinity and low capacity for this metabolite. However, when the mucosa was washed extensively before homogenization, a 3.7S macromolecule was consistently observed which showed considerable specificity and affinity for 1,25-dihydroxyvitamin D3. Although 3.7S binders for 1,25-dihydroxyvitamin D3 could also be located in other organs, competition experiments with excess nonradioactive 1,25-dihydroxyvitamin D3 suggested that they were not identical to the 3.7S macromolecule from intestinal mucosal cytosol. As the 3.7S macromolecule was allowed to stand at 4 °C with bound 1,25-dihydroxy-[3H]vitamin D3, the 1,25-dihydroxy-[3H]vitamin D3 became increasingly resistant to displacement by non-radioactive 1,25-dihydroxyvitamin D3. The 1,25-dihydroxy-[3H]vitamin D3 remained unchanged and easily extractable with lipid solvents through this change, making unlikely the establishment of a covalent bond. Unlike the chick, mucosa from rats yielded cytosol in which no specific binding of 1,25-dihydroxy-[3H]vitamin D3 was detected. Instead, a 5-6S macromolecule which binds both 1,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 was found. This protein which was also found in chick mucosa shows preferential binding for 25-hydroxyvitamin D3. It could be removed by washing the mucosa with buffer prior to homogenization which suggests that it may not be a cytosolic protein. Although the 3.7S protein from chick mucosa has properties consistent with its possible role as a receptor, the 5-6S macromolecule does not appear to have “receptor”-like properties. 相似文献
19.
We investigated the occurrence of rickets in adolescent tamarins (Saguinus imperator) residing at the Los Angeles Zoo. Compared to tamarins in the same colony without clinical evidence of bone disease (N = 6), rachitic platyrrhines (N = 3) had a decrease in their serum calcium concentration (P < .05). The affected tamarins also had lower serum 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) levels than did nonaffected colony mates, but 2–10-fold higher concentrations than in Old World primates of a comparable developmental stage. New World primates in many different genera are known to exhibit target organ resistance to the active vitamin D3 metabolite, 1,25-(OH)2D3, compensated by maintenance of high circulating concentrations of 1,25-(OH)2D3. The relatively low serum 1,25-(OH)2D3 concentration in rachitic tamarins and ultraviolet B radiation deficient environment of these primates suggested that bone disease may be linked to a deficiency in substrate for 1,25-(OH)2D3, 25 hydroxyvtamin D3 (25-OHD3). Chronic exposure of platyrrhines in three different vitamin D resistant genera to an artificial UVB source resulted in 1) a significant increase in the mean serum 25-OHD3 (P < .001) and 1,25-(OH)2D3 (P < .02) level over that encountered in platyrrhines not exposed to UVB; and 2) prevention of rachitic bone disease in irradiated individuals. These data further show that the serum 25-OHD3 and 1,25-OH2D3 levels are positively correlated in vitamin D-resistant platyrrhines (r = 0.64; P= .0014) and suggest that a compromise in cutaneous vitamin D3 production by means of UVB deprivation may limit necessary 1,25-(OH)2D3 production. © 1992 Wiley-Liss, Inc. 相似文献
20.
K. van der Meijden N. Bravenboer N.F. Dirks A.C. Heijboer M. den Heijer G.M.J. de Wit C. Offringa P. Lips R.T. Jaspers 《Journal of cellular physiology》2016,231(11):2517-2528
An adequate vitamin D status is essential to optimize muscle strength. However, whether vitamin D directly reduces muscle fiber atrophy or stimulates muscle fiber hypertrophy remains subject of debate. A mechanism that may affect the role of vitamin D in the regulation of muscle fiber size is the local conversion of 25(OH)D to 1,25(OH)2D by 1α‐hydroxylase. Therefore, we investigated in a murine C2C12 myoblast culture whether both 1,25(OH)2D3 and 25(OH)D3 affect myoblast proliferation, differentiation, and myotube size and whether these cells are able to metabolize 25(OH)D3 and 1,25(OH)2D3. We show that myoblasts not only responded to 1,25(OH)2D3, but also to the precursor 25(OH)D3 by increasing their VDR mRNA expression and reducing their proliferation. In differentiating myoblasts and myotubes 1,25(OH)2D3 as well as 25(OH)D3 stimulated VDR mRNA expression and in myotubes 1,25(OH)2D3 also stimulated MHC mRNA expression. However, this occurred without notable effects on myotube size. Moreover, no effects on the Akt/mTOR signaling pathway as well as MyoD and myogenin mRNA levels were observed. Interestingly, both myoblasts and myotubes expressed CYP27B1 and CYP24 mRNA which are required for vitamin D3 metabolism. Although 1α‐hydroxylase activity could not be shown in myotubes, after treatment with 1,25(OH)2D3 or 25(OH)D3 myotubes showed strongly elevated CYP24 mRNA levels compared to untreated cells. Moreover, myotubes were able to convert 25(OH)D3 to 24R,25(OH)2D3 which may play a role in myoblast proliferation and differentiation. These data suggest that skeletal muscle is not only a direct target for vitamin D3 metabolites, but is also able to metabolize 25(OH)D3 and 1,25(OH)2D3. J. Cell. Physiol. 231: 2517–2528, 2016. © 2016 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc. 相似文献