scholarly journals Beneficial Regulation of Cellular Oxidative Stress Effects, and Expression of Inflammatory, Angiogenic, and the Extracellular Matrix Remodeling Proteins by 1α,25-Dihydroxyvitamin D3 in a Melanoma Cell Line

Molecules ◽  
2020 ◽  
Vol 25 (5) ◽  
pp. 1164
Author(s):  
Neena Philips ◽  
Philips Samuel ◽  
Thomas Keller ◽  
Asma Alharbi ◽  
Samar Alshalan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Superoxide Dismutase ◽  
Promoter Activity ◽  
Membrane Damage ◽  
Melanoma Cells ◽  
Dihydroxyvitamin D3 ◽  
Ecm Remodeling ◽  
Stress Effects ◽  
Tnf Α ◽  
Rna Damage

The causes of cancer include the cellular accumulation reactive oxygen species (ROS), which overrides the cellular antioxidants such as superoxide dismutase, from intrinsic aging, genetics, and exposure to environmental pollutants and ultraviolet (UV) radiation. The ROS damage biomolecules such as DNA (including p53 gene), RNA, and lipids, and activate inflammatory, angiogenic, and extracellular matrix (ECM) remodeling proteins; which collectively facilitate carcinogenesis. The 1α,25-dihydroxyvitamin D3 (Vitamin D) has anti-carcinogenic potential from its antioxidant, anti-inflammatory, and endocrine properties. We examined the anti-carcinogenic mechanism of vitamin D through the beneficial regulation of oxidative stress effects (oxidative DNA/RNA damage, superoxide dismutase expression, membrane damage, and p53 promoter activity), and expression (at the protein, mRNA and/or promoter levels) of inflammatory mediators (interleukin-1 (IL-1) and tumor necrosis factor-α (TNF-α)), angiogenic mediators (transforming growth factor-β (TGF-β), and vascular endothelial growth factor (VEGF)), and the ECM remodeling proteins (matrix metalloproteinases (MMP)-1 and MMP-2) by vitamin D in melanoma cells. Vitamin D inhibited oxidative DNA/RNA damage and membrane damage; and stimulated superoxide dismutase expression and p53 promoter activity in melanoma cells. It inhibited the expression of IL-1, TNF-α, TGF-β, VEGF, MMP-1 and MMP-2 by transcriptional or post-transcriptional mechanisms. We conclude that vitamin D is beneficial to melanoma cells through the inhibition of oxidative DNA/RNA damage, membrane damage, and the expression of inflammatory, angiogenic and ECM remodeling proteins; and the stimulation of superoxide dismutase expression and p53 promoter activity.

Inhibitory effect of NF-κB on 1,25-dihydroxyvitamin D3 and retinoid X receptor function

2000 ◽  
Vol 279 (1) ◽  
pp. E213-E220 ◽  
Author(s):  
Paul K. Farmer ◽  
Xiaofei He ◽  
M. Lienhard Schmitz ◽  
Janet Rubin ◽  
Mark S. Nanes
Keyword(s):  
Vitamin D ◽  
Dna Sequences ◽  
Transcriptional Activation ◽  
Inhibitory Effect ◽  
Retinoid X Receptor ◽  
Mobility Shift ◽  
Dihydroxyvitamin D3 ◽  
Dihydroxyvitamin D ◽  
Tnf Α ◽  
Factor Α

Responsiveness to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] may be diminished in osteoporosis and inflammatory arthritis. The inflammatory cytokine tumor necrosis factor-α (TNF-α) is produced in excess in these disorders and has been shown to decrease osteoblast transcriptional responsiveness to vitamin D and to inhibit the binding of the vitamin D receptor (VDR) and its nuclear partner the retinoid X receptor (RXR) to DNA. Previous studies have shown that a vitamin D (VDRE) or retinoid X DNA response element (RXRE) is sufficient to confer TNF-α inhibition of vitamin D or retinoid-stimulated transcription in the absence of known TNF-α-responsive DNA sequences. We tested the hypothesis that the TNF-α-stimulated transcription factor nuclear factor (NF)-κB could, in part, mediate TNF-α action by inhibiting the transcriptional potency of the VDR and RXR at their cognate cis regulatory sites. Osteoblastic ROS 17/2.8 cells transfected with a dose of NF-κB comparable to that stimulated by TNF-α decreased 1,25(OH)2D3-stimulated transcription. This inhibitory effect of NF-κB was not observed on basal transcription of a heterologous reporter in the absence of the VDRE. The effects of NF-κB and TNF-α were comparable but not additive. COS-7 cells were cotransfected with reporters under the regulation of VDRE or RXRE along with vectors expressing VDR, RXR, and NF-κB nuclear proteins. Reconstituted NF-κB and the NF-κB subunit p65 alone, but not p50, dose dependently suppressed basal and ligand-stimulated transcription. p65 overexpression completely abrogated enhanced VDRE-mediated transcriptional activity in response to 1,25(OH)2D3. Electrophoretic mobility shift experiments did not reveal a direct effect of recombinant NF-κB or its individual subunits on the binding of heterodimeric VDR-RXR to DNA. These results suggest that TNF-α inhibition of hormone-stimulated transcriptional activation may be mediated by activation of NF-κB. In contrast, the inhibitory effect of TNF-α on binding of receptors to DNA is unlikely to be mediated by NF-κB and is not necessary for inhibition of transcription.

scholarly journals Ferrotoxicity and Its Amelioration by Calcitriol in Cultured Renal Cells

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Chandrashekar Annamalai ◽  
Rohit Seth ◽  
Pragasam Viswanathan
Keyword(s):  
Lipid Peroxidation ◽  
Vitamin D ◽  
Superoxide Dismutase ◽  
Iron Content ◽  
Vero Cells ◽  
Renal Cells ◽  
Dihydroxyvitamin D3 ◽  
Total Thiol ◽  
1,25 Dihydroxyvitamin D3

Globally, acute kidney injury (AKI) is associated with significant mortality and an enormous economic burden. Whereas iron is essential for metabolically active renal cells, it has the potential to cause renal cytotoxicity by promoting Fenton chemistry-based oxidative stress involving lipid peroxidation. In addition, 1,25-dihydroxyvitamin D3 (calcitriol), the active form of vitamin D, is reported to have an antioxidative role. In this study, we intended to demonstrate the impact of vitamin D on iron-mediated oxidant stress and cytotoxicity of Vero cells exposed to iohexol, a low osmolar iodine-containing contrast media in vitro. Cultured Vero cells were pretreated with 1,25-dihydroxyvitamin D3 dissolved in absolute ethanol (0.05%, 2.0 mM) at a dose of 1 mM for 6 hours. Subsequently, iohexol was added at a concentration of 100 mg iodine per mL and incubated for 3 hours. Total cellular iron content was analysed by a flame atomic absorption spectrophotometer at 372 nm. Lipid peroxidation was determined by TBARS (thiobarbituric acid reactive species) assay. Antioxidants including total thiol content were assessed by Ellman’s method, catalase by colorimetric method, and superoxide dismutase (SOD) by nitroblue tetrazolium assay. The cells were stained with DAPI (4 ′ ,6-diamidino-2-phenylindole), and the cytotoxicity was evaluated by viability assay (MTT assay). The results indicated that iohexol exposure caused a significant increase of the total iron content in Vero cells. A concomitant increase of lipid peroxidation and decrease of total thiol protein levels, catalase, and superoxide dismutase activity were observed along with decreased cell viability in comparison with the controls. Furthermore, these changes were significantly reversed when the cells were pretreated with vitamin D prior to incubation with iohexol. Our findings of this in vitro model of iohexol-induced renotoxicity lend further support to the nephrotoxic potential of iron and underpin the possible clinical utility of vitamin D for the treatment and prevention of AKI.

1α,25-Dihydroxyvitamin D3 targeting of NF-κB suppresses TNF-α induced adhesion molecules expression in human endothelial cells

2019 ◽  
Author(s):  
Qingyan Zhang ◽  
Yuan Feng ◽  
Yishan Zhou ◽  
Cheng Sun ◽  
Wei Zhu ◽  
...  
Keyword(s):  
Vitamin D ◽  
Endothelial Cells ◽  
Western Blot ◽  
Adhesion Molecules ◽  
Nuclear Translocation ◽  
Active Form ◽  
Chip Assay ◽  
Human Endothelial Cells ◽  
Dihydroxyvitamin D3 ◽  
Tnf Α

Abstract Background Vitamin D and its analogues have been documented to be associated with endothelial dysfunction in various diseases. However, the underlying mechanism remains unknown. Here, we conducted an in vitro study to evaluate the effect of 1α,25-dihydroxyvitamin D3, the active form of vitamin D, on adhesion molecules expression in human endothelial cells. The possible mechanism involved in this process was also explored.Methods Human umbilical vein cells (HUVECs) were cultured and treated according to the experiment requirement. Western Blot and RT-PCR were used to evaluate the expression of vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. ChIP assay, immunofluorescence, Western Blot and co-immunoprecipitation were used to assess the effect of 1α,25-dihydroxyvitamin D3 on NF-κB signaling.Results 1α,25-dihydroxyvitamin D3 inhibited VCAM-1 and E-selectin mRNA and protein expression after TNF-α stimulation. ChIP assay showed that TNF-α increased the p65 binding to the promoter of VCAM-1 and E-selectin, which was suppressed by 1α,25-dihydroxyvitamin D3. 1α,25-dihydroxyvitamin D3 affected TNF-α induced IκBα phosphorylation and p65 NF-κB activation, leading to an inhibition of p65 nuclear translocation. These effects were reversed by a specific vitamin D receptor siRNA (VDR-siRNA). Co-immunoprecipitation revealed that 1α,25-dihydroxyvitamin D3 induced an increased binding of VDR to p65, which inhibited the ability of p65 binding to target gene promoters.Conclusions 1,25-dihydroxyvitamin D3 suppresses TNF-α induced adhesion molecules expression in human endothelial cells by blocking the NF-κB pathway, and this was VDR dependent.

scholarly journals Effects of 60-Day Saccharomyces boulardii and Superoxide Dismutase Supplementation on Body Composition, Hunger Sensation, Pro/Antioxidant Ratio, Inflammation and Hormonal Lipo-Metabolic Biomarkers in Obese Adults: A Double-Blind, Placebo-Controlled Trial

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2512
Author(s):  
Mariangela Rondanelli ◽  
Niccolò Miraglia ◽  
Pietro Putignano ◽  
Ignazio Castagliuolo ◽  
Paola Brun ◽  
...  
Keyword(s):  
Vitamin D ◽  
Superoxide Dismutase ◽  
Body Composition ◽  
Uric Acid ◽  
Fat Mass ◽  
Intervention Group ◽  
Saccharomyces Boulardii ◽  
Homa Index ◽  
Obese Adults ◽  
Hunger Sensation

In animals it has been demonstrated that Saccharomyces boulardii and Superoxide Dismutase (SOD) decrease low-grade inflammation and that S. boulardii can also decrease adiposity. The purpose of this study was to evaluate the effect of a 60-day S. boulardii and SOD supplementation on circulating markers of inflammation, body composition, hunger sensation, pro/antioxidant ratio, hormonal, lipid profile, glucose, insulin and HOMA-IR, in obese adults (BMI 30–35 kg/m2). Twenty-five obese adults were randomly assigned to intervention (8/4 women/men, 57 ± 8 years) or Placebo (9/4 women/men, 50 ± 9 years). Intervention group showed a statistically significant (p < 0.05) decrease of body weight, BMI, fat mass, insulin, HOMA Index and uric acid. Patients in intervention and control groups showed a significant decrease (p < 0.05) of GLP-1. Intervention group showed an increase (p < 0.05) of Vitamin D as well. In conclusion, the 60-day S. boulardii-SOD supplementation in obese subjects determined a significant weight loss with consequent decrease on fat mass, with preservation of fat free mass. The decrease of HOMA index and uric acid, produced additional benefits in obesity management. The observed increase in vitamin D levels in treated group requires further investigation.

scholarly journals Regulation of TREM1-Mediated Inflammation in Hepatocellular Carcinoma Cells

Reports ◽  
2021 ◽  
Vol 4 (2) ◽  
pp. 17
Author(s):  
Vikrant Rai ◽  
Devendra K. Agrawal
Keyword(s):  
Hepatocellular Carcinoma ◽  
Vitamin D ◽  
Chronic Inflammation ◽  
Therapeutic Target ◽  
Primary Liver Cancer ◽  
Migration And Invasion ◽  
Potential Therapeutic Target ◽  
Mediators Of Inflammation ◽  
Tnf Α ◽  
Hcc Cells

Hepatocellular carcinoma (HCC), accounting for more than 90% of cases of primary liver cancer, is the third most common cause of cancer-related death worldwide. Chronic inflammation precedes the development of cirrhosis and HCC. TREM (triggering receptor expressed on myeloid cell)-1 is an inflammatory marker and amplifier of inflammation that signals through PI3K and ERK1/2 to activate transcription factors, resulting in increased secretion of pro-inflammatory cytokines, causing chronic inflammation and predisposing the liver to carcinogenesis. Thus, targeting TREM-1 in HCC might be a potential therapeutic target. A low level of vitamin D has been associated with chronic inflammation and poor prognosis in HCC. Thus, we evaluated the effect of vitamin D on TREM-1 expression in the HCC cell line. Additionally, the effects of high mobility group box-1, lipopolysaccharide, and transcription factor PU.1 on the expression of TREM-1 in normal liver cells and HCC cells have been investigated in the presence and absence of vitamin D. The results showed increased expression of TREM-1 in HCC cells and with IL-6, TNF-α, LPS, and rHMGB-1 and decreased expression with calcitriol. Calcitriol also attenuated the effect of IL-6, TNF-α, LPS, and rHMGB-1 on TREM-1. Calcitriol treatment attenuated the proliferation, migration, and invasion of HCC cells. These results (in vitro) provide molecular and biochemical evidence that calcitriol significantly attenuates the expression of mediators of inflammation, and thus might be used therapeutically together with conventional treatment to delay the progression of HCC. Additionally, the negative regulation of TREM-1 by PU.1 suggests PU.1 as a potential therapeutic target.

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