The activity of integrins on leukocytes is kept under tight control to avoid inappropriate adhesion while these cells are circulating in blood or migrating through tissues. Using lymphocyte function-associated antigen-1 (LFA-1) on T cells as a model, we have investigated adhesion to ligand intercellular adhesion molecule-1 induced by the Ca2+ mobilizers, ionomycin, 2, 5-di-t-butylhydroquinone, ...

Oxidative stress is implicated in the pathogenesis of pancreatic β-cell dysfunction that occurs in both type 1 and type 2 diabetes. Nuclear factor E2-related factor 2 (NRF2) is a master regulator in the cellular adaptive response to oxidative stress. The present study found that MIN6 β-cells with stable knockdown of Nrf2 (Nrf2-KD) and islets isolated from Nrf2-knockout mice expressed substantia...

Induction of phase 2 detoxification enzymes by phenolic antioxidants can account for prevention of tumor initiation but cannot explain why these compounds inhibit tumor promotion. Phase 2 genes are induced through an antioxidant response element (ARE). Although the ARE resembles an AP-1 binding site, we show that the major ARE binding and activating protein is not AP-1. Interestingly, AP-1 DNA ...

Drinking water contaminated with arsenic, a human carcinogen, is a worldwide health issue. An understanding of cellular signaling events in response to arsenic exposure and rational designing of strategies to reduce arsenic damages by modulating signaling events are important to fight against arsenic-induced diseases. Previously, we reported that activation of the Nrf2-mediated cellular defense...

Interactions among transcription factors control their physiological functions by regulating their binding specificities and transcriptional activities.We implement a strategy tovisualize directly the genomic loci that are bound bymulti-protein complexes in single cells inDrosophila. This method is based on bimolecular fluorescence complementation (BiFC) analysis of protein interactions on poly...

Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphorylcholine (OxPAPC) is present in oxidative modified LDL and accumulates in lesions of many chronic inflammatory diseases, such as atherosclerosis. In a microarray study, OxPAPC has been demonstrated to modulate the expression of >700 genes in human aortic endothelial cells. We found that the levels of mRNA for OKL38 [also named Bone marro...

Glucocorticoids regulate the rat glutathione S-transferase A2 (GSTA2) gene in a biphasic manner in cultured hepatocytes that repress gene expression at low concentration (10--100 nM) but induce gene expression at high concentration (>1 microM). High concentrations of the glucocorticoid receptor (GR) antagonist RU38486 (5--10 microM) also induced the expression of GSTA2. These effects were repro...

Epithelial mucous membranes are repeatedly exposed to oxidants and xenobiotics. CFTR plays a role in glutathione transepithelial flux and in defining the hydration and viscoelasticity of protective mucus. We therefore hypothesized that CFTR expression and function may be modulated by oxidant stress. A sublethal oxidant stress (tert-butylhydroquinone, BHQ) in CFTR-expressing epithelial cells (T8...

Human colon carcinoma Caco-2 cells were used to study the induction of UDP glucuronosyltransferase (UGT) isoforms UGT1A6, UGT1A9, and UGT2B7 by aryl hydrocarbon receptor agonists and by antioxidant-type inducers with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and t-butylhydroquinone (TBHQ), respectively. Early- (PF11) and late-passage clones (TC7) of Caco-2 cells, which show low and high consti...

The liver is the main organ of drug metabolism, but the expression and induction by xenobiotics of drug-metabolizing enzymes is also often observed in extrahepatic tissues. Recently, we reported that lipophilic cytochrome P450 inducers, beta-naphthoflavone (BNF), phenobarbital, and dexamethasone, induced CYP1, CYP2B, and CYP3A enzymes, respectively, in rat epididymal white adipose tissue (WAT) ...