Thioredoxin (Trx) and thioredoxin reductase 1 (TR1) are among the major redox regulators in mammalian cells and have a wide variety of roles, including removal of intracellular reactive oxygen species (ROS) and prevention of cell death. Tumor necrosis factor-α (TNF-α) induces cancer cell death. Although ROS have been proposed to participate in this process, the role of the thioredoxin system in...

Thioredoxin reductase 1 (TR1) is a major redox regulator in mammalian cells. As an important antioxidant selenoprotein, TR1 is thought to participate in cancer prevention, but is also known to be over-expressed in many cancer cells. Numerous cancer drugs inhibit TR1, and this protein has been proposed as a target for cancer therapy. We previously reported that reduction of TR1 levels in cancer ...

AIM To evaluate and compare the expression of thioredoxin reductase 1 (TrxR1) in primary and secondary glioblastoma samples. MATERIAL AND METHODS Surgically resected human glioblastoma samples from 40 patients who underwent surgery at our institution were extracted from their histopathological specimens and divided into three groups. Ten histopathologically regular cerebral tissue samples, ac...

Selenium is an essential trace element in mammals, but is toxic at high levels. It is best known for its cancer prevention activity, but cancer cells are more sensitive to selenite toxicity than normal cells. Since selenite treatment leads to oxidative stress, and the Trx (thioredoxin) system is a major antioxidative system, we examined the interplay between TR1 (Trx reductase 1) and Trx1 defic...

Glucose regulatory protein (GRP58) is known to mediate mitomycin C (MMC)-induced DNA cross-linking. However, the mechanism remains elusive. We hypothesized that thioredoxin-like domains, one at NH2 terminus and another at COOH terminus, are required for GRP58-mediated MMC reductive activation leading to DNA cross-linking. Site-directed mutagenesis mutated cysteines in thioredoxin domains to ser...

Pyrroloquinoline quinone (PQQ) is a redox active cofactor for bacterial quinoproteins. Dietary PQQ also has prominent physiological effects in mammals although no mammalian quinoprotein has yet been conclusively identified. Here we found that PQQ has substantial effects on the redox active mammalian selenoprotein thioredoxin reductase 1 (TrxR1). PQQ efficiently inhibited the activity of TrxR1 w...

Multiple myeloma (MM) is a hematological malignancy characterized by the aberrant accumulation of clonal plasma cells in the bone marrow. Despite recent advancement in anti-myeloma treatment, MM remains an incurable disease. This study showed higher intrinsic oxidative stress and higher Trx1 and TrxR1 protein levels in MM cells compared to normal cells. Drug-induced Trx1 (PX-12) and TrxR1 (Aura...

Dietary selenium intake has been linked to reduced cancer risk, however the underlying mechanisms are yet unknown. We question the commonly used practice of applying selenium concentrations found in human blood to in vitro studies and evaluated the utility of biomarkers, e.g., glutathione peroxidase 1 (GPx1) and thioredoxin reductase 1 (TrxR1), to determine appropriate selenium levels for in vi...

The biological activities of propolis are varied from plant sources and the prominent antioxidant effects of Chinese propolis (poplar type) have been extensively reported. Oxidative stress is associated with inflammation and induces many diseases. In the study, to evaluate antioxidant capacities and clarify the underlying molecular mechanisms of ethanol extracts of Chinese propolis (EECP) and e...

Human cornea is highly susceptible to damage by dust. Continued daily exposure to housedust has been associated with increasing risks of corneal injury, however, the underlying mechanism has not been elucidated. In this study, a composite housedust sample was tested for its cytotoxicity on primary human corneal epithelial (PHCE) cells, which were exposed to dust at 5-320μg/100μL for 24h. PHCE c...