Proc Natl Acad Sci U S A
July 2024
Upon encountering allergens, CD4 T cells differentiate into IL-4-producing Th2 cells in lymph nodes, which later transform into polyfunctional Th2 cells producing IL-5 and IL-13 in inflamed tissues. However, the precise mechanism underlying their polyfunctionality remains elusive. In this study, we elucidate the pivotal role of NRF2 in polyfunctional Th2 cells in murine models of allergic asthma and in human Th2 cells.
View Article and Find Full Text PDFWe observed that treatment with dimethyl α-ketoglutarate (DMK) increased the amount of intracellular α-ketoglutarate significantly more than that of α-ketoglutarate in HaCaT cells. DMK also increased the level of intracellular 4-hydroxyproline and promoted the production of collagen in HaCaT cells. In addition, DMK decreased the production of collagenase and elastase and down-regulated the expression of selected matrix metalloproteinases (MMPs), such as MMP-1, MMP-9, MMP-10, and MMP-12, via transcriptional inhibition.
View Article and Find Full Text PDFItaconate is a metabolite produced to counteract and resolve pro-inflammatory responses when macrophages are challenged with intracellular or extracellular stimuli. In the present study, we have observed that dimethyl itaconate (DMI) inhibits melanogenesis in B16F10 cells. DMI inhibits microphthalmia-associated transcription factor (MITF) and downregulates the expression of MITF target genes, such as tyrosinase (TYR), tyrosinase-related protein 1 (TRP-1), and tyrosinase-related protein 2 (TRP-2).
View Article and Find Full Text PDFis known to inhibit the development and progression of many age-related diseases, but the underlying molecular mechanisms are largely unclear. In the present study, we observed that the ethanol extract of scavenged 2,2'-diphenylpicrylhydrazyl and 2,2'-azinobis diammonium radicals in vitro. The ethanol extract of activated antioxidant response element-luciferase activity and induced expression of NRF2 target genes in HaCaT cells.
View Article and Find Full Text PDFSubsequently to the publication of the above article, an interested reader drew to the authors' attention that certain of the data panels featured in Figs. 1B, 4A, 6A and 8A, showing DAPI or NAC staining of the cells, appeared to contain overlapping data. The authors have consulted their original data, and realize that errors were made during the compilation of these figures; consequently, they have repeated the affected experiments.
View Article and Find Full Text PDFKELCH-ECH-associated protein 1 (KEAP1) is an adaptor protein of Cullin 3 (CUL3) E3 ubiquitin ligase that targets a redox sensitive transcription factor, NF-E2-related factor 2 (NRF2). BRCA1-associated protein 1 (BAP1) is a tumor suppressor and deubiquitinase whose mutations increase the risk of several types of familial cancers. In the present study, we have identified that BAP1 deubiquitinates KEAP1 by binding to the BTB domain.
View Article and Find Full Text PDFWe have identified triptolide as a novel NRF2 inhibitor, which significantly attenuates ARE-luciferase activity at nanomolar concentrations. Triptolide did not affect the level of NRF2, but significantly inhibited the expression of NRF2 target genes in A549 cells. We found that NRF2 possesses a previously unrecognized NES in the Neh2 domain, and that triptolide promotes an interaction between NRF2 and CRM1.
View Article and Find Full Text PDFBackground: A wide range of environmental factors, such as diseases, nutritional deficiencies, ageing, hormonal imbalances, stress, and ultraviolet (UV) radiation, may affect the structure and function of the skin that covers the entire surface of the human body. In this study, we investigated roles of red ginseng oil (RGO) in enhancing skin functions, including hair growth and skin protection, using mouse models.
Methods: For hair growth experiment, shaved dorsal skins of C57BL/6 mice were topically applied with vehicle, RGO, RGO's major compounds, or minoxidil for consecutive 21 days and skin tissues were examined the hair growth promoting capacity.
Background: Coptisine is a natural alkaloid compound and is known to have multiple beneficial effects including antioxidant activity. However, whether it can protect lung fibroblasts from oxidative damage has not been studied yet.
Objectives: To investigate the potential inhibitory effect of coptisine against oxidative stress in V79-4 lung fibroblast cells.
Non-alcoholic fatty liver disease (NAFLD) causes liver dysfunction and is associated with obesity and type 2 diabetes. Chronic inflammation is associated not only with the development of NAFLD, but also with hepatic diseases, including steatohepatitis, cirrhosis, and hepatocellular carcinoma. Auranofin is a treatment for rheumatoid arthritis and has recently been reported to have potential effects against a variety of diseases, including inflammation, cancer, and viral infection.
View Article and Find Full Text PDFThe skin is constantly exposed to various types of chemical stresses that challenge the immune cells, leading to the activation of T cell-mediated hypersensitivity reactions including atopic dermatitis. Previous studies have demonstrated that a variety of natural compounds are effective against development of atopic dermatitis by modulating immune responses. Cardamonin is a natural compound abundantly found in cardamom spices and many other medicinal plant species.
View Article and Find Full Text PDFBackground: Oysters () are a popular marine product worldwide and have the advantage of nutritional benefits. This study aimed to investigate the effect of fermented oyster extract (FO) on growth promotion, including analysis of body size, bone microarchitecture, hematology and biochemistry .
Methods: The amount of nutrients and gamma aminobutyric acid (GABA) were determined.
Biochem Pharmacol
July 2020
NF-E2-related factor 2 (NRF2) is a master regulator of redox homeostasis and provides cellular protection against oxidants and electrophiles by inducing the expression of a wide array of phase II cytoprotective genes. Until now, a number of NRF2 activators have been developed for treatment of chronic diseases and some are under evaluation in the clinical studies. On the other hand, accumulating evidence indicates that NRF2 confers chemoresistance and radioresistance, and its expression is correlated with poor prognosis in cancer patients.
View Article and Find Full Text PDFFree Radic Res
December 2020
Tumors adapt well to the imbalanced redox status created by rapid growth and limited nutrient availability because they highly express high levels of NRF2 to counteract oxidative stress. Therefore, inhibition of NRF2 is currently considered a feasible strategy for development of chemotherapeutic agents. In the present study, we identified that Na/K-ATPase regulates NRF2 in A549 cells.
View Article and Find Full Text PDFNRF2 is a redox-sensitive transcription factor that plays an important role in protecting organisms against diverse types of electrophiles or oxidants. The level of NRF2 is maintained low in normal cells, but highly elevated in cancer provoking chemoresistance or radioresistance. It is now recognized that NRF2 does not merely maintain the redox balance, but also plays significant roles in autophagy, apoptosis, cell cycle progression, and stem cell differentiation, all of which could be possibly attributable to the existence of multiple binding proteins.
View Article and Find Full Text PDFHomoharringtonine, known as omacetaxine mepesuccinate, is a pharmaceutical drug substance approved for treatment of chronic myeloid leukemia. Here, we report that homoharringtonine (HHT) is a novel chemical inhibitor of NRF2. HHT significantly suppressed NRF2 and ARE-dependent gene expression in human lung carcinoma A549 cells.
View Article and Find Full Text PDFWe attempted to examine anti-inflammatory and anti-oxidant effects of 4'-O-β-D-glucosyl-5-O-methylvisamminol (GOMV), the first epigenetic inhibitor of histone phosphorylation at Ser10. While GOMV did not affect the viability of murine macrophage RAW 264.7 cells, it significantly suppressed lipopolysaccharide (LPS)-induced generation of prostaglandin E (PGE) and nitric oxide (NO) through transcriptional inhibition of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS).
View Article and Find Full Text PDFNF-E2-related factor 2 (NRF2) regulates transcription of phase II cytoprotective enzymes to protect normal cells against oxidative stress. However, a high level of NRF2 offers a growth advantage, chemoresistance, and radioresistance in cancer. In the present study, we have identified convallatoxin as a novel inhibitor of NRF2/ARE.
View Article and Find Full Text PDFThe nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a key regulator of gene expression during oxidative stress and drug detoxification. Thus, identifying Nrf2 activators to protect from possible cell damage is necessary. In this study, we investigated whether E--methoxycinnamoyl-α-l-rhamnopyranosyl ester (MCR), a phenylpropanoid isolated from , can activate Nrf2 signaling in human keratinocytes (HaCaT).
View Article and Find Full Text PDFHeme oxygenase-1 (HO-1) catalyzes the enzymatic degradation of heme to produce three anti-oxidant molecules: carbon monoxide (CO), ferrous ion (Fe), and biliverdin. Induction of HO-1 is currently considered as a feasible strategy to treat oxidative stress-related diseases. In the present study, we identified marliolide as a novel inducer of HO-1 in human normal keratinocyte HaCaT cells.
View Article and Find Full Text PDFIn the present study, the effects of the acetonitrile or water extracts from 400 selected traditional medicinal plants on the growth of PC-3 cells were investigated, and it was demonstrated that an acetonitrile extract of Radix exhibited the most marked cytotoxic effects on PC-3 cells. It was observed that the acetonitrile extract of Radix induced marked cell cycle arrest and apoptosis in PC-3 cells through the generation of intracellular reactive oxygen species. It was also demonstrated that oral administration of the acetonitrile extract of Radix decreased the incidence and growth of PC-3 tumor xenografts in nude mice.
View Article and Find Full Text PDFCarboplatin is a less toxic analog of cisplatin, but carboplatin also has side effects, including bone marrow suppression. Therefore, to improve the capacity of the anticancer activity of carboplatin, we investigated whether combined treatment with carboplatin and thioridazine, which has antipsychotic and anticancer activities, has a synergistic effect on apoptosis. Combined treatment with carboplatin and thioridazine markedly induced caspase-mediated apoptosis in head and neck squamous cell carcinoma (AMC-HN4) cells.
View Article and Find Full Text PDFJ Photochem Photobiol B
January 2017
We synthesized a new organic fluorescent dye named resveratrone glucoside from the photoreaction of naturally-occurring phytoalexin compound resveratrol glucoside (resveratrol-3-β-mono-d-glucoside), which is abundant in various plants such as berries, herbs, nuts and grapes. Just like its predecessor molecule resveratrone that was previously discovered by our group, resveratrone glucoside possesses excellent optical properties including a high fluorescence quantum yield, a large Stokes' shift, and a large two-photon absorption cross section. In addition to these highly desirable properties, both fluorescent molecules can also be used as ideal bio-compatible organic fluorophores since they have remarkably low cytotoxicity, which we verified through our cell morphological study, trypan blue exclusion assay, Western blot analysis and fluorescence imaging of various live biological specimens.
View Article and Find Full Text PDFBiomol Ther (Seoul)
November 2016
5-fluorouracil (5-FU) is a chemotherapeutic agent commonly used for treatment of solid tumors, including colorectal cancer. However, chemoresistance against 5-fluorouracil (5-FU) often limits its success for chemotherapy and, therefore, finding out appropriate adjuvant(s) that might overcome chemoresistance against 5-FU bears a significant importance. In the present study, we have found that α-mangostin can sensitize 5-FU-resistant SNUC5/5-FUR colon cancer cells to apoptosis.
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