In vivo detection of phospholipase C by enzyme-activated near-infrared probes.

In this article, the characterization of the first near-infrared (NIR) phospholipase-activated molecular beacon is reported, and its utility for in vivo cancer imaging is demonstrated. The probe consists of three elements: a phospholipid (PL) backbone to which the NIR fluorophore, pyropheophorbide a (Pyro), and the NIR Black Hole Quencher 3 (BHQ) were conjugated. Because of the close proximity of BHQ to Pyro, the Pyro-PtdEtn-BHQ probe is self-quenched until enzyme hydrolysis releases the fluorophore.

Phenylbutyrate induces apoptosis and lipid accumulations via a peroxisome proliferator-activated receptor gamma-dependent pathway.

The effects of the selective peroxisome proliferator activated receptor-gamma (PPAR-gamma) inhibitor GW9662 on phenylbutyrate (PB)-induced NMR-detectable lipid metabolites was investigated on DU145 prostate cancer cells. DU145 cells were perfused with 10 mM PB in the presence or absence of 1 microM of GW9662 and the results monitored by (31)P and diffusion-weighted (1)H NMR spectroscopy. GW9662 completely reversed PB-induced NMR-visible lipid and total choline accumulation in (1)H spectra and glycerophosphocholine and beta-NTP in (31)P spectra.

Lovastatin enhances phenylbutyrate-induced MR-visible glycerophosphocholine but not apoptosis in DU145 prostate cells.

In this study the effects of lovastatin on DU145 prostate cancer cells treated with phenylbutyrate (PB) was investigated in order to determine the NMR-detectable metabolic changes resulting from the cooperative activity of these two agents. DU145 cells were perfused with PB in the presence or absence of 10 microM of the HMG-CoA reductase inhibitor lovastatin, and the results monitored by 31P and diffusion-weighted 1H NMR spectroscopy. Lovastatin had additive effects on the PB-induced NMR-visible total choline in 1H spectra, and glycerophosphocholine in 31P spectra but no significant effect on NMR-visible lipid.

Increases in NMR-visible lipid and glycerophosphocholine during phenylbutyrate-induced apoptosis in human prostate cancer cells.

DU145 human prostatic carcinoma cells were treated with the differentiating agents phenylacetate (PA) and phenylbutyrate (PB) and examined in perfused cultures by diffusion-weighted 1H and 31P nuclear magnetic resonance spectroscopy (NMR). PA and PB (10 mM) induced significant (>3-fold) time-dependent increases in the level of NMR-visible lipids and total choline in 1H spectra, and glycerophosphocholine levels in the 31P spectra, with the increases being greater for PB. These effects were accompanied by significant increases in cytoplasmic lipid droplets and intracellular lipid volume fraction as observed by morphometric analysis of Oil Red O-stained cells.

Engineered Saccharomyces cerevisiae strain BioS-1, for the detection of water-borne toxic metal contaminants.

Saccharomyces cerevisiae responds to extracellular toxic stimuli by increasing intracellular cyclic AMP levels, leading to activation of a cAMP-dependent protein kinase, protein kinase A (PKA). Activated PKA phosphorylates downstream substrates, including specific DNA-binding proteins, to turn off the expression of most or all of the yeast genes. Such cAMP-PKA-mediated inhibition of gene expression in response to toxic stimuli appears to be unique to S.

A New Class of Supramolecular, Mixed-Metal DNA-Binding Agents: The Interaction of Ru(II),Pt(II) and Os(II),Pt(II) Bimetallic Complexes with DNA.

A new type of mixed-metal, supramolecular complex has been designed that incorporates a platinum center to allow binding to DNA. The interaction of two such platinum heterobimetallic complexes of the general formula [(bpy)(2)M(dpb)PtCl(2)]Cl(2) (M = Ru(II), Os(II); bpy = 2,2'-bipyridine; dpb = 2,3-bis(2-pyridyl)benzoquinoxaline) with DNA is reported herein. The modular design of these systems allows for synthetic variation of individual components within this structural motif.