OBJECTIVES To determine whether or not the antioxidants N-acetylcysteine (NAC) and allopurinol (ALP) confer synergistic cardioprotection against myocardial ischemia/reperfusion (MI/R) injury by stabilizing hypoxia inducible factor 1α (HIF-1α)/heme oxygenase 1 (HO-1) signaling in diabetic myocardium. METHODS Control or diabetic [streptozotocin (STZ)-induced] Sprague Dawley rats received vehicl...

We investigated the effects of PGC-1α (peroxisome proliferator-activated receptor γ coactivator-1α) overexpression on the oxidative capacity of human skeletal muscle cells ex vivo. PGC-1α overexpression increased the oxidation rate of palmitic acid and mRNA expression of genes regulating lipid metabolism, mitochondrial biogenesis, and function in human myotubes. Basal and insulin-stimulated deo...

Introduction: Hypoxia-inducible factor-1 (HIF-1) is a heterodimer made up of an oxygen-regulated HIF-1α subunit and a constitutively expressed HIF-1β subunit. Under hypoxic conditions, HIF-1α is stabilized and binds to hypoxia response elements that act as transcriptional controls of several genes. Among the 70 target genes of HIF-1 known so far, several are involved in angiogenesis, cell proli...

Hepatocellular carcinoma (HCC) is one of the most frequent primary malignancies of the liver and is resistant to anticancer drugs. Hypoxia is a master cause of tumor resistance to chemotherapy. Hypoxia-inducible factor-one alpha (HIF-1α) plays a key role in the adaptive responses to hypoxic environments. HIF-1α is constitutively up-regulated in several tumor types might thus be implicated in tu...

OBJECTIVE Hypoxia-inducible factor 1 alpha regulates genes related to cellular survival under hypoxia. This factor is present in osteroarthritic chondrocytes, and cytokines, such as interleukin-1 beta, participate in the pathogenesis of osteoarthritis, thereby increasing the activities of proteolytic enzymes, such as matrix metalloproteinases, and accelerating cartilage destruction. We hypothes...

Mucus secretion is often uncontrolled in many airway inflammatory diseases of humans. Identifying the regulatory pathway(s) of mucus gene expression, mucus overproduction, and hypersecretion is important to alleviate airway inflammation in these diseases. However, the regulatory signaling pathway controlling mucus overproduction has not been fully identified yet. In this study, we report that t...

Transcriptional coactivators and corepressors often have multiple targets and can have opposing actions on transcription and downstream physiological events. The coactivator peroxisome proliferator-activated receptor-γ coactivator (PGC)-1α is under-expressed in Huntington's disease and is a regulator of antioxidant defenses and mitochondrial biogenesis. We show that in primary cortical neurons,...

Human peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) is a key coactivator in the regulation of gene transcriptional activity in normal tissues. However, it is not clear whether it is involved in the angiogenesis and metabolism of multiple myeloma (MM). The aim of the present study was to investigate the role of PGC-1α in MM. Small interfering RNA (siRNA) was used to inhibi...

Mesenchymal stem cells (MSC) secrete paracrine factors that may exert a protective effect on the heart after coronary artery occlusion. This study was done to determine the effect of hypoxia and serum levels on the mRNA expression and secretion of paracrine factors. Mouse bone marrow MSC were cultured with 5% or 20% serum and in either normoxic (21% O2) or hypoxic (1% O2) conditions. Expression...

Hypoxia-inducible factor-1α (HIF-1α) induces tumor proliferation, angiogenesis and metastasis. Reactive oxygen species, hypoxia, and growth factor stimulation induce HIF-1α, and the augmented HIF-1α activity confers upon cancer cells the ability to adapt to microenvironments. Oltipraz is a cancer chemopreventive agent and has an inhibitory effect on angiogenesis and tumor growth. Nonetheless, t...