A5090109773- Vitamin D Research Studies
- Estrogen and related hormone effects
- Skin Protection and Aging
- Circadian rhythm and melatonin
- Hormonal Regulation and Hypertension
- Psoriasis: Treatment and Pathogenesis
- melanin and skin pigmentation
- Vitamin C and Antioxidants Research
- Olfactory and Sensory Function Studies
- Acne and Rosacea Treatments and Effects
- Stress Responses and Cortisol
- Dermatology and Skin Diseases
- Adrenal Hormones and Disorders
- Birth, Development, and Health
- Computational Drug Discovery Methods
- Biotin and Related Studies
- Cannabis and Cannabinoid Research
- Cholesterol and Lipid Metabolism
- Steroid Chemistry and Biochemistry
- Cancer Immunotherapy and Biomarkers
- Dermatological and Skeletal Disorders
- RNA Research and Splicing
- Biosimilars and Bioanalytical Methods
- Adipose Tissue and Metabolism
- Cytokine Signaling Pathways and Interactions
University of Alabama at Birmingham
2016-2025
Birmingham VA Medical Center
2015-2017
University of Tennessee Health Science Center
2004-2015
University of Alabama
2015
Center for Cancer Research
2009-2014
Ducks Unlimited
2013
The University of Western Australia
2011-2013
Curtin University
2011
Bruker (United States)
2011
We define previously unrecognized in vivo pathways of vitamin D3 (D3) metabolism generating novel D3-hydroxyderivatives different from 25-hydroxyvitamin [25(OH)D3] and 1,25(OH)2D3. Their products include 20-hydroxyvitamin [20(OH)D3], 22(OH)D3, 20,23(OH)2D3, 20,22(OH)2D3, 1,20(OH)2D3,1,20,23(OH)3D3, 17,20,23(OH)3D3 were produced by placenta, adrenal glands, epidermal keratinocytes. detected the predominant metabolite [20(OH)D3] human serum with a relative concentration ~20 times lower than...
RORα and RORγ are expressed in human skin cells that produce the noncalcemic 20-hydroxyvitamin D3 [20(OH)D3] 20,23-dihydroxyvitamin [20,23(OH)2D3]. Chinese hamster ovary (CHO) stably expressing a Tet-on or expression vector ROR-responsive element (RORE)-LUC reporter, mammalian 2-hybrid model examining interaction between ligand binding domain (LBD) of with an LBD-interacting LXXLL-peptide, were used to study ROR-antagonist activities. These assays revealed 20(OH)D3 20,23(OH)2D3 function as...
Melanoma, originating through malignant transformation of melanin-producing melanocytes, is a formidable malignancy, characterized by local invasiveness, recurrence, early metastasis, resistance to therapy, and high mortality rate. This review discusses etiologic risk factors for melanoma, diagnostic prognostic tools, including recent advances in molecular biology, omics, bioinformatics, provides an overview its therapy. Since the incidence melanoma rising remains unacceptably high, we...
Indolic and kynuric pathways of skin melatonin metabolism were monitored by liquid chromatography mass spectrometry in human keratinocytes, melanocytes, dermal fibroblasts, melanoma cells. Production 6-hydroxymelatonin [6(OH)M], N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) 5-methoxy-tryptamine (5-MT) was detected a cell type-dependent fashion. The major metabolites, 6(OH)M AFMK, produced all Thus, immortalized epidermal (HaCaT) the product with Vmax = 63.7 ng/106 cells Km 10.2 μM, lower...
Background Cytochrome P450scc metabolizes vitamin D3 to 20-hydroxyvitamin (20(OH)D3) and 20,23(OH)2D3, as well 1-hydroxyvitamin 1α,20-dihydroxyvitamin (1,20(OH)2D3). It also cleaves the side chain of 7-dehydrocholesterol producing 7-dehydropregnenolone (7DHP), which can be transformed 20(OH)7DHP. UVB induces transformation steroidal 5,7-dienes pregnacalciferol (pD) a lumisterol-like compounds (pL). Methods Findings To define biological significance these P450scc-initiated pathways, we tested...
Ultraviolet light (UV) is an inducer of reactive oxygen species (ROS) as well 6-4-photoproducts and cyclobutane pyrimidine dimers (CPD) in the skin, which further cause damage to skin cells. Irradiation cultured human melanocytes with UVB stimulated ROS production, was reduced cells treated melatonin or its metabolites: 6-hydroxymelatonin (6-OHM), N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), N-acetylserotonin (NAS), 5-methoxytryptamine (5-MT). Melatonin derivatives also expression NRF2...
We tested whether novel CYP11A1-derived vitamin D3- and lumisterol-hydroxyderivatives, including 1,25(OH)2D3, 20(OH)D3, 1,20(OH)2D3, 20,23(OH)2D3, 1,20,23(OH)3D3, lumisterol, 20(OH)L3, 22(OH)L3, 20,22(OH)2L3, 24(OH)L3, can protect against UVB-induced damage in human epidermal keratinocytes. Cells were treated with above compounds for 24 h, then subjected to UVB irradiation at doses of 25, 50, 75, or 200 mJ/cm2, examined oxidant formation, proliferation, DNA damage, the expression genes mRNA...
A novel pathway of vitamin D activation by CYP11A has previously been elucidated. To define the mechanism action its major dihydroxy-products, we tested divergence and overlap between gene expression profiles human epidermal keratinocytes treated with either CYP11A1-derived 20,23(OH)₂D3 or classical 1,25(OH)₂D3. Both secosteroids have significant chemical similarity only differences being positions hydroxyl groups. mRNA was isolated examined microarray analysis using Illumina's HumanWG-6...
We investigated the protective effects of melatonin and its metabolites: 6-hydroxymelatonin (6-OHM), N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK), N-acetylserotonin (NAS), 5-methoxytryptamine (5-MT) in human keratinocytes against a range doses (25, 50, 75 mJ/cm2) ultraviolet B (UVB) radiation. There was significant reduction generation reactive oxygen species (50-60%) when UVB-exposed were treated with or derivatives. Similarly, metabolites reduced nitrite hydrogen peroxide levels that...
Melatonin and its derivatives (N1 -acetyl-N2 -formyl-5-methoxykynurenine [AFMK] N-acetyl serotonin [NAS]) have broad-spectrum protective effects against photocarcinogenesis, including both direct indirect antioxidative actions, regulation of apoptosis DNA damage repair; these data were primarily derived from in vitro models. This study evaluates possible beneficial melatonin active ultraviolet B (UVB)-induced harm to human porcine skin ex vivo cultured HaCaT cells. The topical application...
Abstract The interactions of derivatives lumisterol (L3) and vitamin D3 (D3) with liver X receptors (LXRs) were investigated. Molecular docking using crystal structures the ligand binding domains (LBDs) LXRα β revealed high scores for L3 hydroxymetabolites, similar to those natural ligands, predicting good receptor. RNA sequencing murine dermal fibroblasts stimulated D3-hydroxyderivatives LXR as second nuclear receptor pathway several D3-hydroxyderivatives, including 1,25(OH) 2 D3. This was...
CYP11A1 and CYP27A1 hydroxylate tachysterol3, a photoproduct of previtamin D3, producing 20S-hydroxytachysterol3 [20S(OH)T3] 25(OH)T3, respectively. Both metabolites were detected in the human epidermis serum. Tachysterol3 was also serum at concentration 7.3 ± 2.5 ng/ml. 20S(OH)T3 25(OH)T3 inhibited proliferation epidermal keratinocytes dermal fibroblasts stimulated expression differentiation anti-oxidative genes similar manner to 1,25-dihydroxyvitamin D3 [1,25(OH)2D3]. They acted on vitamin...
Melatonin is widely present in Nature. It has pleiotropic activities, part mediated by interactions with high-affinity G-protein-coupled melatonin type 1 and 2 (MT1 MT2) receptors or under extreme conditions, e.g., ischemia/reperfusion. In pharmacological concentrations, it given to counteract the massive damage caused MT1- MT2-independent mechanisms. The aryl hydrocarbon receptor (AhR) a perfect candidate for mediating latter effects because structural similarity its natural ligands,...
Vitamin D is a natural photoproduct that has many beneficial effects on different organs, including skin. Active forms of vitamin and its derivatives exert biological skin cells, thus maintaining homeostasis. In keratinocytes, they inhibit proliferation stimulate differentiation, have anti-inflammatory properties, act as antioxidants, DNA damage repair after ultraviolet (UV) exposure. melanocytes, also cell proliferation, apoptosis antioxidants. fibroblasts, affect fibrotic processes...
The side chain of vitamin D3 is hydroxylated in a sequential manner by cytochrome P450scc (CYP11A1) to form 20-hydroxycholecalciferol, which can induce growth arrest and differentiation both primary immortalized epidermal keratinocytes. Since nuclear factor-kappaB (NF-kappaB) plays pivotal role the regulation cell proliferation, apoptosis, we examined capability 20-hydroxycholecalciferol modulate activity NF-kappaB, using 1,25-dihydroxycholecalciferol (calcitriol) as positive control....