Alprazolam is a hypnotic/tranquilizer that has been shown to specifically inhibit the platelet-activating factor (PAF)-induced aggregation of human platelets. The goal of this study was to elucidate whether alprazolam modulates IL-1alpha-initiated responses. For this purpose we investigated the effects of alprazolam on the IL-1alpha-induced production of inflammatory cytokines (IL-8 and monocyt...

The expressions of hypoxia-inducible genes are upregulated by hypoxia-inducible factor 1 (HIF-1), which is a heterodimer of HIF-1alpha and HIF-1beta/ARNT (aryl hydrocarbon receptor nuclear transporter). Under hypoxic conditions, HIF-1alpha becomes stabilized and both HIF-1alpha and ARNT are translocated into the nucleus and codimerized, binding to the HIF-1 consensus sequence and transactivatin...

IL-1 molecules are encoded by two distinct genes, IL-1alpha and IL-1beta. Both isoforms possess essentially identical activities and potencies, whereas IL-1alpha, in contrast to IL-1beta, is known to act as a membrane-associated IL-1 (MA-IL-1) and plays an important role in a variety of inflammatory situations. The transgenic (Tg) mouse line (Tg1706), which was generated in our laboratory, over...

OBJECTIVES To explore mechanisms through which altered peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) expression may influence Alzheimer disease (AD) amyloid neuropathology and to test the hypothesis that promotion of PGC-1alpha expression in neurons might be developed as a novel therapeutic strategy in AD. DESIGN Case-control. Patients Human postmortem brain...

THE acyl carrier coenzyme A (CoA) is involved in fatty acid metabolism. The carnitine/CoA ratio is of particular importance in regulating the transport of long-chain fatty acids into mitochondria for oxidation. Also CoA has a role in the formation and breakdown of products from both the cyclooxygenase and lipoxygenase pathways of the precursor arachidonic acid. In the present study the effect o...

Tissue invasion by tumor cells involves their migration across basement membranes through activation of extracellular matrix degradation and cell motility mechanisms. Chemokines binding to their receptors provide chemotactic cues guiding cells to specific tissues and organs; they therefore could potentially participate in tumor cell dissemination. Melanoma cells express CXCR4, the receptor for ...

Translation requires the specific attachment of amino acids to tRNAs by aminoacyl-tRNA synthetases (aaRSs) and the subsequent delivery of aminoacyl-tRNAs to the ribosome by elongation factor 1 alpha (EF-1alpha). Interactions between EF-1alpha and various aaRSs have been described in eukaryotes, but the role of these complexes remains unclear. To investigate possible interactions between EF-1alp...

Phagocytosis is the process by which microbial pathogens are engulfed by macrophages and neutrophils and represents the first line of defense against bacterial infection. The importance of phagocytosis for bacterial clearance is of particular relevance to systemic inflammatory diseases, which are associated with the development of hypoxia, yet the precise effects of hypoxia on phagocytosis rema...

Neuroprotective properties of ketosis may be related to the upregulation of hypoxia inducible factor (HIF)-1alpha, a primary constituent associated with hypoxic angiogenesis and a regulator of neuroprotective responses. The rationale that the utilization of ketones by the brain results in elevation of intracellular succinate, a known inhibitor of prolyl hydroxylase (the enzyme responsible for t...

To identify novel regulatory factors controlling induction of the brown adipocyte-specific mitochondrial uncoupling protein (Ucp1) mRNA in the retroperitoneal white fat depot, we previously mapped quantitative trait loci (QTLs) that control this trait to chromosomes 2, 3, 8, and 19. Since the peroxisome proliferator activator receptor-gamma coactivator-1alpha (PGC-1alpha) regulates Ucp1 and oth...