A5028221691- Mechanisms of cancer metastasis
- Plant Genetic and Mutation Studies
- melanin and skin pigmentation
- Mitochondrial Function and Pathology
- Cancer Mechanisms and Therapy
- CRISPR and Genetic Engineering
- DNA Repair Mechanisms
- Skin Protection and Aging
- Metabolism and Genetic Disorders
- Retinal Diseases and Treatments
- Retinal Development and Disorders
- Advanced biosensing and bioanalysis techniques
- Redox biology and oxidative stress
- Peptidase Inhibition and Analysis
- Circadian rhythm and melatonin
- Polyamine Metabolism and Applications
- Cell Adhesion Molecules Research
- DNA and Nucleic Acid Chemistry
- Melanoma and MAPK Pathways
- Trace Elements in Health
- Immunotherapy and Immune Responses
- Connexins and lens biology
- Retinopathy of Prematurity Studies
- Cancer-related Molecular Pathways
- Glaucoma and retinal disorders
University of Kentucky
2012-2021
Markey Cancer Center
2012-2021
Molecular Oncology (United States)
2013
University of Cape Town
2013
Charles University
2013
University of Tennessee Health Science Center
2011
Roswell Park Comprehensive Cancer Center
2011
Inserm
2011
The Graduate Center, CUNY
2011
University of Colorado Anschutz Medical Campus
2008
Exposure of biological chromophores to ultraviolet radiation can lead photochemical damage. However, the role visible light, particularly in blue region spectrum, has been largely ignored. To test hypothesis that light is toxic non-pigmented epithelial cells, confluent cultures human primary retinal cells were exposed (390-550 nm at 2.8 milliwatts/cm2) for up 6 h. A small loss mitochondrial respiratory activity was observed h compared with dark-maintained and this became greater increasing...
The ketogenic diet (KD) is a high-fat, low carbohydrate that used as therapy for intractable epilepsy. However, the mechanism(s) by which KD achieves neuroprotection and/or seizure control are not yet known. We sought to determine whether improves mitochondrial redox status. Adolescent Sprague-Dawley rats (P28) were fed or 3 weeks and ketosis was confirmed plasma levels of beta-hydroxybutyrate (BHB). KD-fed showed twofold increase in hippocampal GSH GSH/GSSG ratios compared with diet-fed...
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...
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...
Mitochondria are critical for ocular function as they represent the major source of a cell’s supply energy and play an important role in cell differentiation survival. Mitochondrial dysfunction can occur result inherited mitochondrial mutations (e.g. Leber’s hereditary optic neuropathy chronic progressive external ophthalmoplegia) or stochastic oxidative damage which leads to cumulative is factor age-related disorders macular degeneration, cataract diabetic retinopathy). DNA (mtDNA)...
Reduced expression of the metastasis suppressor NM23-H1 is associated with aggressive forms multiple cancers. Here, we establish that (termed H1 isoform in human, M1 mouse) and two its attendant enzymatic activities, 3'-5' exonuclease nucleoside diphosphate kinase, are novel participants cellular response to UV radiation (UVR)-induced DNA damage. deficiency compromised kinetics repair for total polymerase-blocking lesions nucleotide excision (6-4) photoproducts vitro. Kinase activity was...
Chelatable iron is an important catalyst for the initiation and propagation of free radical reactions implicated in pathogenesis diverse neuronal disorders. Studies our laboratory have shown that mitochondria are principal source reactive oxygen species production after status epilepticus (SE). We asked whether SE modulates mitochondrial levels by two independent methods consequent dysfunction injury could be ameliorated with a cell-permeable chelator. Kainate-induced resulted time-dependent...
Blunted melanocortin 1 receptor (MC1R) signaling promotes melanocyte genomic instability in part by attenuating cAMP-mediated DNA repair responses, particularly nucleotide excision (NER), which recognizes and clears mutagenic photodamage. cAMP-enhanced NER is mediated interactions between the ataxia telangiectasia-mutated Rad3-related (ATR) xeroderma pigmentosum complementation group A (XPA) proteins. We now report a critical role for sirtuin (SIRT1) regulating ATR-mediated phosphorylation...
The aims of this study were; (i) to elucidate the mechanisms involved in determining cell type-specific responses oxidative stress and (ii) test hypothesis that types which are subjected high burdens vivo, have greater resistance. Cultures retinal pigment epithelium (RPE), corneal fibroblasts, alveolar type II skin epidermal cells were studied. Cellular sensitivity H2O2 was determined by MTT assay. antioxidant status (CuZnSOD, MnSOD, GPX, CAT) analyzed with enzymatic assays susceptibility...
Cutaneous malignant melanoma is the most lethal form of skin cancer, with 5-year survival rates <5 % for patients presenting metastatic disease. Mechanisms underlying spread UVR-induced are not well understood, in part due to a paucity animal models that accurately recapitulate disease its advanced forms. We have employed transgenic mouse strain harboring tandem deletion nm23-m1 and nm23-m2 genes assess combined contribution these suppression metastasis. Crossing nm23-h1/nm23-h2 knockout...
Abstract Loss-of-function in melanocortin 1 receptor (MC1R), a GS protein-coupled that regulates signal transduction through cAMP and protein kinase A (PKA) melanocytes, is major inherited melanoma risk factor. Herein, we report novel cAMP-mediated response for sensing responding to UV-induced DNA damage regulated by A-kinase-anchoring 12 (AKAP12). AKAP12 identified as necessary participant PKA-mediated phosphorylation of ataxia telangiectasia mutated Rad3-related (ATR) at S435,...
<i>Purpose:</i> To investigate the role of poly(ADP-ribose)-polymerase (PARP) in protecting against oxidative (H<sub>2</sub>O<sub>2</sub>) and alkylation (MMS) damage to nDNA mtDNA genomes retinal pigment epithelium (RPE). We further hypothesized that PARP ribosylation enzymatic activity is required facilitate efficient repair enable RPE survive chronic stress exposure. <i>Methods:</i> Cellular sensitivity...
Abstract Homozygous loss of function the melanocortin 1 receptor (MC1R) is associated with a pheomelanotic pigment phenotype and increased melanoma risk. MC1R heterozygosity less well studied, although individuals inheriting one loss‐of‐function allele are also melanoma‐prone. Using K14‐Scf C57BL/6J animal model whose skin characterized by lifelong retention interfollicular epidermal melanocytes like that human, we studied pigmentary, UV responses, DNA repair capacity in variant Mc1r...