Search results for "NF-E2-Related Factor 2"
showing 10 items of 34 documents
Living with stress: regulation of antioxidant defense genes in the subterranean, hypoxia-tolerant mole rat, Spalax.
2011
Lack of oxygen is life threatening for most mammals. It is therefore of biomedical interest to investigate the adaptive mechanisms which enable mammalian species to tolerate extremely hypoxic conditions. The subterranean mole rat Spalax survives substantially longer periods of hypoxia than the laboratory rat. We hypothesized that genes of the antioxidant defense, detoxifying harmful reactive oxygen species generated during hypoxia and hyperoxia, are involved in Spalax underground adaptation. Using quantitative RT-PCR, we analyzed the mRNA expression levels of seven antioxidant defense genes (catalase, glutathione peroxidase 1, glutathione-S-transferase Pi1, heme oxygenase 1, superoxide dism…
Chemical and biochemical responses to sub−lethal doses of mercury and cadmium in gilthead seabream (Sparus aurata)
2022
Specimens of Sparus aurata were exposed to sub-lethal concentrations of Hg and Cd for 25 days and the levels of both metals were investigated in organs and tissues. Bioaccumulation of Hg decreased as follow: gills > kidney > liver > skin > muscle, while the order of Cd bioaccumulation was: liver > kidney > gills > skin > muscle. Immediately after exposure, both metals showed the highest bioaccumulation in gills and skin indicating that these organs are reliable targets for biomonitoring studies after short term exposure. Metals introduction caused a significant time-dependent concentrations increase in kidney and liver, while in the muscle a significant in-crease of …
Transcription factor NRF2 regulates miR-1 and miR-206 to drive tumorigenesis
2013
The mechanisms by which deregulated nuclear factor erythroid-2–related factor 2 (NRF2) and kelch-like ECH-associated protein 1 (KEAP1) signaling promote cellular proliferation and tumorigenesis are poorly understood. Using an integrated genomics and 13C-based targeted tracer fate association (TTFA) study, we found that NRF2 regulates miR-1 and miR-206 to direct carbon flux toward the pentose phosphate pathway (PPP) and the tricarboxylic acid (TCA) cycle, reprogramming glucose metabolism. Sustained activation of NRF2 signaling in cancer cells attenuated miR-1 and miR-206 expression, leading to enhanced expression of PPP genes. Conversely, overexpression of miR-1 and miR-206 decreased the exp…
Cajaninstilbene acid (CSA) exerts cytoprotective effects against oxidative stress through the Nrf2-dependent antioxidant pathway.
2013
Cajaninstilbene acid (CSA), an active compound separated from pigeon pea leaves, possesses the highly efficient antioxidant activities. Transcription factor nuclear factor-erythroid 2-related factor 2 (Nrf2) is an important regulator of cellular oxidative stress. This study examined the role of Nrf2 in CSA-mediated antioxidant effects on human hepatocarcinoma (HepG2) cell line. The generation of reactive oxygen species (ROS) upon H2O2 and CSA treatment was lower than that of H2O2 alone. CSA activated Nrf2 as evaluated by Western blotting. A luciferase reporter assay also demonstrated that CSA-activated signaling resulted in the increased transcriptional activity of Nrf2 through binding to t…
Pterostilbene Prevents Early Diabetic Retinopathy Alterations in a Rabbit Experimental Model
2019
Oxidative stress generated by diabetes plays a key role in the development of diabetic retinopathy (DR), a common diabetic complication. DR remains asymptomatic until it reaches advanced stages, which complicate its treatment. Although it is known that good metabolic control is essential for preventing DR, knowledge of the disease is incomplete and an effective treatment with no side effects is lacking. Pterostilbene (Pter), a natural stilbene with good antioxidant activity, has proved to beneficially affect different pathologies, including diabetes. Therefore, our study aimed to analyse the protective and/or therapeutic capacity of Pter against oxidant damage by characterising early retina…
Activation of p38, p21, and NRF-2 Mediates Decreased Proliferation of Human Dental Pulp Stem Cells Cultured under 21% O2
2014
Summary High rates of stem cell proliferation are important in regenerative medicine and in stem cell banking for clinical use. Ambient oxygen tensions (21% O2) are normally used for in vitro culture, but physiological levels in vivo range between 3% and 6% O2. We compared proliferation of human dental pulp stem cells (hDPSCs) cultured under 21% versus 3% O2. The rate of hDPSC proliferation is significantly lower at 21% O2 compared to physiological oxygen levels due to enhanced oxidative stress. Under 21% O2, increased p38 phosphorylation led to activation of p21. Increased generation of reactive oxygen species and p21 led to activation of the NRF-2 signaling pathway. The upregulation of NR…
Molecular mechanisms of hepatotoxic cholestasis by clavulanic acid: Role of NRF2 and FXR pathways.
2021
Treatment of β-lactamase positive bacterial infections with a combination of amoxicillin (AMOX) and clavulanic acid (CLAV) causes idiosyncratic drug-induced liver injury (iDILI) in a relevant number of patients, often with features of intrahepatic cholestasis. This study aims to determine serum bile acid (BA) levels in amoxicillin/clavulanate (A + C)-iDILI patients and to investigate the mechanism of cholestasis by A + C in human in vitro hepatic models. In six A + C-iDILI patients, significant elevations of serum primary conjugated BA definitely demonstrated A + C-induced cholestasis. In cultured human Upcyte hepatocytes and HepG2 cells, CLAV was more cytotoxic than AMOX, and, at subcytoto…
Loss of Nrf2 in bone marrow-derived macrophages impairs antigen-driven CD8+ T cell function by limiting GSH and Cys availability
2015
NF-E2-related factor 2 (Nrf2), known to protect against reactive oxygen species, has recently been reported to resolve acute inflammatory responses in activated macrophages. Consequently, disruption of Nrf2 promotes a proinflammatory macrophage phenotype. In the current study, we addressed the impact of this macrophage phenotype on CD8(+) T cell activation by using an antigen-driven coculture model consisting of Nrf2(-/-) and Nrf2(+/+) bone marrow-derived macrophages (BMDMΦ) and transgenic OT-1 CD8(+) T cells. OT-1 CD8(+) T cells encode a T cell receptor that specifically recognizes MHC class I-presented ovalbumin OVA(257-264) peptide, thereby causing a downstream T cell activation. Interes…
Modulation of Nrf2/ARE pathway by food polyphenols: a nutritional neuroprotective strategy for cognitive and neurodegenerative disorders
2011
In recent years, there has been a growing interest, supported by a large number of experimental and epidemi-ological studies, for the beneficial effects of some phenolic substances, contained in commonly used spices and herbs, in preventing various age-related pathologic conditions, ranging from cancer to neurodegenerative diseases. Although the exact mechanisms by which polyphenols promote these effects remain to be elucidated, several reports have shown their ability to stimulate a general xenobiotic response in the target cells, activating multiple defense genes. Data from our and other laboratories have previously demonstrated that curcumin, the yellow pigment of curry, strongly induces…
ROS-Dependent ER Stress and Autophagy Mediate the Anti-Tumor Effects of Tributyltin (IV) Ferulate in Colon Cancer Cells
2020
Organotin compounds represent potential cancer therapeutics due to their pro-apoptotic action. We recently synthesized the novel organotin ferulic acid derivative tributyltin (IV) ferulate (TBT-F) and demonstrated that it displays anti-tumor properties in colon cancer cells related with autophagic cell death. The purpose of the present study was to elucidate the mechanism of TBT-F action in colon cancer cells. We specifically show that TBT-F-dependent autophagy is determined by a rapid generation of reactive oxygen species (ROS) and correlated with endoplasmic reticulum (ER) stress. TBT-F evoked nuclear factor erythroid-2 related factor 2 (Nrf2)-mediated antioxidant response and Nrf2 silenc…