On the conformational dependence of the proton chemical shifts in nucleosides and nucleotides III. Proton chemical shifts of 5′-nucleotides as a function of different conformational parameters

The variation of the chemical shift of the protons of 5′-UMP and 5′-AMP is calculated as a function of χ_CN, ψ and ? torsion angles. The shift of H8 of 5′-AMP and H6 of 5′-UMP is found to be very sensitive to the value of χ_CN. For the anti conformations the shift of these protons is more sensitive to the value of the rotation about CS′-05′ than about C4′-CS′. For the protons of the ribose the calculations show that for the C2′-endo pucker H3′ and H2′ undergo the largest chemical shift variations when ? and ψ vary. The calculated variations are considered in relation with the role of the conformation of the nucleotides in the chemical shift variation between mono and polynucleotides and between the different helical structures of polynucleotides.     

Liver copper content of rats hypo- or hyperresponsive to dietary cholesterol

The question addressed is whether cholesterol intake reduces the hepatic copper content in rats. For this purpose we have compared the hepatic copper content of two selected rat inbred strains after feeding the animals a control or a high fat, high cholesterol diet. One strain was dietary cholesterol resistant (SHR/OlaIpcv), whereas the other strain was susceptible to dietary cholesterol (BN-Lx/Cub). Dietary cholesterol-susceptible rats have a lower baseline hepatic copper content when compared with their resistant counterparts. The consumption of a hypercholesterolemic diet decreased the liver copper concentration (expressed in microg/g dry weight) to about the same extent in both strains. However, dietary cholesterol did not reduce the absolute (expressed as microg/whole liver) and relative (expressed as microg/whole liver/100 g body weight) copper store of rats. The decrease of liver copper concentration after the high fat, high cholesterol diet is probably not caused by a decrease in whole hepatic copper content, but rather due to dietary-induced hepatomegaly.     

Nox5 mediates PDGF-induced proliferation in human aortic smooth muscle cells

The proliferation of vascular smooth muscle cells is important in the pathogenesis of many vascular diseases. Reactive oxygen species (ROS) produced by NADPH oxidases in smooth muscle cells have been shown to participate in signaling cascades regulating proliferation induced by platelet-derived growth factor (PDGF), a powerful smooth muscle mitogen. We sought to determine the role of Nox5 in the regulation of PDGF-stimulated human aortic smooth muscle cell (HASMC) proliferation. Cultured HASMC were found to express four isoforms of Nox5. When HASMC stimulated with PDGF were pretreated with N-acetyl cysteine (NAC), proliferation was significantly reduced. Proliferation induced by PDGF was also heavily dependent on JAK/STAT activation, as the JAK inhibitor, AG490, was able to completely abolish PDGF-stimulated HASMC growth. Specific knockdown of Nox5 with a siRNA strategy reduced PDGF-induced HASMC ROS production and proliferation. Additionally, siRNA to Nox5 inhibited PDGF-stimulated JAK2 and STAT3 phosphorylation. ROS produced by Nox5 play an important role in PDGF-induced JAK/STAT activation and HASMC proliferation.