Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30044 (antioxidant enzyme)
 8,037 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Breathing air exposes humans and other mammals to various toxic agents including oxidative contaminants associated with fine particles of less than 2.5 micron which may be deposited in the deep lung and have been implicated in the increased morbidity and mortality correlated with air pollution. Oxidative damage from inhaled particles may include damage to DNA, thereby adversely affecting the immunosurveillance provided by alveolar macrophages. Using the rat alveolar macrophage cell line NR8383, we demonstrated that cell proliferation was inhibited by exogenous hydrogen peroxide, an oxidant naturally produced in cellular respiration and phagocytosis. Mercaptosuccinate, a specific inhibitor of the antioxidant enzyme glutathione peroxidase, also inhibited cell growth. Genes known to be coordinatively regulated in response to growth arrest and DNA damage, GADD45 and GADD153, were induced compared to the housekeeping gene beta-ACTIN by equitoxic doses of hydrogen peroxide and mercaptosuccinate. Hydrogen peroxide treatment of cells in which glutathione peroxidase was inhibited by mercaptosuccinate resulted in even greater induction of both GADD genes. This approach using the NR8383 alveolar macrophage cell line provides a model for studying genotoxicity at the mechanistic level at which stress-responsive genes involved in growth arrest and DNA-damage response are modulated.
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PMID:NR8383 alveolar macrophage toxic growth arrest by hydrogen peroxide is associated with induction of growth-arrest and DNA damage-inducible genes GADD45 and GADD153. 935 15

Rhododenol or rhododendrol (RD, 4-(4-hydroxyphenyl)-2-butanol) occurs naturally in many plants along with raspberry ketone (RK, 4-(4-hydroxyphenyl)-2-butanone), a ketone derivative, which include Nikko maple tree (Acer nikoense) and white birch (Betula platyphylla). De-pigmenting activity of RD was discovered and it was used as a brightening ingredient for the skin whitening cosmetics. Recently, cosmetics containing RD were withdrawn from the market because a number of consumers developed leukoderma, inflammation and erythema on their face, neck and hands. Here, we explored the mechanism underlying the toxicity of RD and RK against melanocytes using B16F10 murine melanoma cells and human primary epidermal melanocytes. Treatment with RD or RK resulted in the decreased cell viability in a dose-dependent manner which appeared from cell growth arrest. Consistently, ROS generation was significantly increased by RD or RK as determined by DCF-enhanced fluorescence. An antioxidant enzyme, glutathione peroxidase was depleted as well. In line with ROS generation, oxidative damages and the arrest of normal cell proliferation, GADD genes (Growth Arrest and DNA Damage) that include GADD45 and GADD153, were significantly up-regulated. Prevention of ROS generation with an anti-oxidant, N-acetylcysteine (NAC) significantly rescued RD and RK-suppressed melanocyte proliferation. Consistently, up-regulation of GADD45 and GADD153 was significantly attenuated by NAC, suggesting that increased ROS and the resultant growth arrest of melanocytes may contribute to RD and RK-induced leukoderma.
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PMID:Rhododenol and raspberry ketone impair the normal proliferation of melanocytes through reactive oxygen species-dependent activation of GADD45. 2686 44