Noninvasive imaging of cell death using an Hsp90 ligand.

Cell death plays a central role in normal physiology and in disease. Common to apoptotic and necrotic cell death is the eventual loss of plasma membrane integrity. We have produced a small organoarsenical compound, 4-(N-(S-glutathionylacetyl)amino)phenylarsonous acid, that rapidly accumulates in the cytosol of dying cells coincident with loss of plasma membrane integrity.

Structural determinants for the interaction of lipopolysaccharide binding protein with purified high density lipoproteins: role of apolipoprotein A-I.

The interaction of lipopolysaccharide binding protein (LBP) with apolipoprotein (apo)A-I on high density lipoproteins (HDL) was studied in solid phase ligand binding assays with a biotinylated LBP-specific antibody. The association was dependent on LBP concentration and enhanced in the presence of lipopolysaccharide (LPS). Maximal enhancement was measured at an LPS/LBP molar ratio of 6.

A direct role for protein kinase C and the transcription factor Jun/AP-1 in the regulation of the Alzheimer's beta-amyloid precursor protein gene.

Overexpression of the beta-amyloid precursor protein gene (beta-APP) may contribute to the abnormal generation of beta-amyloid protein in Alzheimer's disease. We demonstrate using a human glial cell line (1321N1) that activation of protein kinase C (PKC) with phorbol 12-myristate 13-acetate (PMA) increases beta-APP mRNA levels, induces known components of the transcription factor activator protein-1 (AP-1), and increases protein-DNA binding activity to AP-1 sequences within the beta-APP promoter. A beta-APP promoter-luciferase reporter gene is transcriptionally activated by PMA, as well as by expression of constitutively activated PKC or by expression of c-Jun.

Induction of c-fos mRNA expression in an in vitro hippocampal slice model of adult rats after kainate but not gamma-aminobutyric acid or bicuculline treatment.

Levels of gene expression following in vitro treatment of rat hippocampal slices with kainate, gamma-aminobutyric acid (GABA), or bicuculline were measured by the reverse transcription-coupled polymerase chain reaction method. Following a short-term exposure to kainate, c-fos gene expression was induced by 12-fold in the adult, but not the newborn, hippocampus. Under the same experimental conditions, zifl268 and brain-derived neurotrophic factor (BDNF) gene expression were unchanged.

Sigma receptor ligands inhibit rat tail artery contractile responses by multiple mechanisms.

The goal of this study was to further explore the mechanism of action by which several sigma ligand inhibit vascular contractile responses. By using the rat tail artery, the following sigma receptor ligands were tested: haloperidol; (+)-3-(3-hydroxyphenyl)-N- (1-propyl)piperidine; 1,3-di-ortho-tolyl-guanidine; cis-9- [3-(3,5-dimethyl-1-piperazinyl)propyl]carbazole dihydrochloride; (+/-)-alpha-(4-fluorophenyl)-4-(5-fluoro-2-pyrimidinyl)-1-piperazine butanol; and the two newly identified sigma ligands, N-(1-adamant-1- yl)-N'-(2-iodophenyl)guanidine and 2-amino-(3-phenyl)-3,4-dihydroquinazoline. We first tested the possibility that this inhibitory effect is mediated by an action on muscarinic receptors or an endothelium-dependent mechanism.