The impact of methylmercury on 1,25-dihydroxyvitamin D3-induced transcriptomic responses in dolphin skin cells

2010 ◽  
Vol 391 (2/3) ◽  
Author(s):  
Blake C. Ellis ◽  
Sebastiano Gattoni-Celli ◽  
Mark S. Kindy
Keyword(s):  
Vitamin D ◽  
Target Genes ◽  
Protective Role ◽  
Dihydroxyvitamin D3 ◽  
Skin Cells ◽  
1,25 Dihydroxyvitamin D3 ◽  
Atlantic Bottlenose Dolphin ◽  
Considerable Impact ◽  
The Impact

Abstract The Atlantic bottlenose dolphin has been the focus of much attention owing to the considerable impact of environmental stress on its health and the associated implications for human health. Here, we used skin cells from the dolphin to investigate the protective role of the vitamin D pathway against environmental stressors. We previously reported that dolphin skin cells respond to 1,25-dihydroxyvitamin D3 (1,25D3), the bioactive metabolite of vitamin D3, by upregulation of the vitamin D receptor (VDR) and expression of several genes. Methylmercury is a highly bioaccumulative environmental stressor of relevance to the dolphin. We currently report that in dolphin cells sublethal concentrations of methylmercury compromise the ability of 1,25D3 to upregulate VDR, to transactivate a vitamin D-sensitive promoter, and to express specific target genes. These results help elucidate the effects of vitamin D and methylmercury on innate immunity in dolphin skin and potentially in human skin as well, considering similarities in the vitamin D pathway between the two species.

scholarly journals 1,25-dihydroxyvitamin-D3 but not the clinically applied marker 25-hydroxyvitamin-D3 predicts survival after stem cell transplantation

2020 ◽  
Author(s):  
Katrin Peter ◽  
Peter J. Siska ◽  
Tobias Roider ◽  
Carina Matos ◽  
Heiko Bruns ◽  
...  
Keyword(s):  
Vitamin D ◽  
Stem Cell ◽  
Stem Cell Transplantation ◽  
Cell Transplantation ◽  
Cox Model ◽  
Vitamin D Metabolites ◽  
Vitamin D Status ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
The Impact

Abstract The serum level of 25-hydroxyvitamin-D3 is accepted as marker for a person’s vitamin D status but its role for the outcome of allogeneic hematopoietic stem cell transplantation (HSCT) is controversially discussed. The impact of 1,25-dihydroxyvitamin-D3 on HSCT outcome, however, has never been studied. In a discovery cohort of 143 HSCT patients we repeatedly (day −16 to 100) measured 1,25-dihydroxyvitamin-D3 and in comparison the well-established marker for serum vitamin D status 25-hydroxyvitamin-D3. Only lower 1,25-dihydroxyvitamin-D3 levels around HSCT (day −2 to 7, peritransplant) were significantly associated with higher 1-year treatment-related mortality (TRM) risk (Mann–Whitney U test, P = 0.001). This was confirmed by Cox-model regression without and with adjustment for baseline risk factors and severe acute Graft-versus-Host disease (aGvHD; unadjusted P = 0.001, adjusted P = 0.005). The optimal threshold for 1,25-dihydroxyvitamin-D3 to identify patients at high risk was 139.5 pM. Also in three replication cohorts consisting of altogether 365 patients 1,25-dihydroxyvitamin-D3 levels below 139.5 pM had a 3.3-fold increased risk of TRM independent of severe aGvHD compared to patients above 139.5 pM (Cox-model unadjusted P < 0.0005, adjusted P = 0.001). Our data highlight peritransplant 1,25-dihydroxyvitamin-D3 levels but not the commonly monitored 25-hydroxyvitamin-D3 levels as potent predictor of 1-year TRM and suggest to monitor both vitamin D metabolites in HSCT patients.

scholarly journals Protective Role of Vitamin D in Renal Tubulopathies

Metabolites ◽  
2020 ◽  
Vol 10 (3) ◽  
pp. 115 ◽  
Author(s):  
Guido Gembillo ◽  
Valeria Cernaro ◽  
Rossella Siligato ◽  
Francesco Curreri ◽  
Antonino Catalano ◽  
...  
Keyword(s):  
Vitamin D ◽  
Protective Role ◽  
Inflammatory Factors ◽  
Tubular Injury ◽  
Dihydroxyvitamin D3 ◽  
Damage Response ◽  
Regulation Mechanisms ◽  
Renal Tubular ◽  
The Right

Vitamin D is tightly linked with renal tubular homeostasis: the mitochondria of proximal convoluted tubule cells are the production site of 1α,25-dihydroxyvitamin D3. Patients with renal impairment or tubular injury often suffer from chronic inflammation. This alteration comes from oxidative stress, acidosis, decreased clearance of inflammatory cytokines and stimulation of inflammatory factors. The challenge is to find the right formula for each patient to correctly modulate the landscape of treatment and preserve the essential functions of the organism without perturbating its homeostasis. The complexity of the counter-regulation mechanisms and the different axis involved in the Vitamin D equilibrium pose a major issue on Vitamin D as a potential effective anti-inflammatory drug. The therapeutic use of this compound should be able to inhibit the development of inflammation without interfering with normal homeostasis. Megalin-Cubilin-Amnionless and the FGF23-Klotho axis represent two Vitamin D-linked mechanisms that could modulate and ameliorate the damage response at the renal tubular level, balancing Vitamin D therapy with an effect potent enough to contrast the inflammatory cascades, but which avoids potential severe side effects.

Placental transport of calcium and phosphorus is not regulated by vitamin D

1984 ◽  
Vol 246 (4) ◽  
pp. F526-F529 ◽  
Author(s):  
R. Brommage ◽  
H. F. DeLuca
Keyword(s):  
Vitamin D ◽  
Calcium Content ◽  
Pregnant Rats ◽  
Dihydroxyvitamin D3 ◽  
Fetal Plasma ◽  
Protein Levels ◽  
1,25 Dihydroxyvitamin D3 ◽  
Vitamin D3 Metabolites ◽  
Calcium And Phosphorus

The role of 1,25-dihydroxyvitamin D3 in regulating the maternal-to-fetal transfer of calcium and phosphorus across the placenta was examined by measuring maternal and fetal plasma levels of these elements in vitamin D-replete and -deficient rats. Pregnant rats in their 20th day of gestation and their fetuses were studied. Two diets with different calcium and phosphorus contents were used to produce either hypocalcemia or hypophosphatemia in the vitamin D-deficient rats. Calcium and phosphorus levels in fetal plasma were always higher than maternal values, and in vitamin D deficiency a twofold gradient of calcium and a fivefold gradient of phosphorus concentrations across the placenta were observed. Since protein levels in fetal plasma were approximately fivefold lower than maternal values, protein binding does not account for the higher fetal than maternal concentrations of plasma calcium. These results, together with previous data showing normal calcium content of vitamin D-deficient fetuses, indicate that 1,25-dihydroxyvitamin D3 and other vitamin D3 metabolites are not involved in the active transport of calcium and phosphorus across the placenta in the rat.

A protective role of 1,25-dihydroxyvitamin D3 in chemically induced rat colon carcinogenesis

1992 ◽  
Vol 13 (12) ◽  
pp. 2293-2298 ◽  
Author(s):  
A. Belleli ◽  
S. Shany ◽  
J. Levy ◽  
R. Guberman ◽  
S.A. Lamprecht
Keyword(s):  
Colon Carcinogenesis ◽  
Protective Role ◽  
Rat Colon ◽  
Dihydroxyvitamin D3 ◽  
1,25 Dihydroxyvitamin D3 ◽  
Chemically Induced

Chronic DOCA treatment increases Ca absorption: role of hypercalciuria and vitamin D

1986 ◽  
Vol 251 (3) ◽  
pp. E279-E284 ◽  
Author(s):  
D. Zikos ◽  
C. Langman ◽  
U. Gafter ◽  
B. Delahaye ◽  
K. Lau
Keyword(s):  
Vitamin D ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
High Salt ◽  
High Salt Diet ◽  
Dihydroxyvitamin D3 ◽  
Salt Diet ◽  
1,25 Dihydroxyvitamin D3 ◽  
Best Fit

To examine the effects of mineralocorticoidism on calcium (Ca) absorption and to define the mechanism, rats received a high-salt diet and injections of vehicle or deoxycorticosterone acetate (DOCA). Net (44.2 vs. 31.4 mg/day) and percent Ca absorption (28.1 vs. 20.1%) was increased after 5 days of DOCA. This was associated with increased duodenal 45Ca uptake. Thus despite the hypercalciuria, Ca balance was similar. Although the hypercalciuria persisted chronically, the gut effects were sustained, which maintained normal ionized Ca, bone Ca, and Ca balance. Urinary cyclic adenosine monophosphate was elevated by DOCA. Compared with appropriate controls, neither DOCA alone nor polydipsia (elicited by dextrose) produced similar magnitudes of hypercalciuria as DOCA plus high-salt diet. These maneuvers also failed to increase Ca absorption. Neutralization of the metabolic alkalosis neither attenuated the DOCA-induced hypercalciuria nor abolished the Ca hyperabsorption. In vitamin D-deprived rats, the hypercalciuria but not the intestinal effects of DOCA were reproduced. Serum 1,25-dihydroxyvitamin D3 levels were increased during chronic DOCA treatment (224 vs. 139 pg/ml). These data best fit the hypothesis that increased Ca absorption is secondary to the calciuric effects of DOCA and high-salt diet and is mediated via the increased parathyroid hormone and 1,25-dihydroxyvitamin D3 activities.

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