Dual effect of ceramide on human endothelial cells: induction of oxidative stress and transcriptional upregulation of endothelial nitric oxide synthase.
Background— Generation of the second-messenger molecule ceramide by stimulated sphingomyelinase activity has been implicated in the inflammatory processes contributing to the pathogenesis of atherosclerosis. However, reports of stimulatory effects of ceramide on endothelial NO production in animal models suggest antiatherosclerotic effects of the molecule. Therefore, we investigated long-term effects of ceramide on NO generation in human endothelial cells. Methods and Results— In human umbilical vein endothelial cells (HUVECs) and in HUVEC-derived EA.hy 926 endothelial cells, C6-ceramide ( N -hexanoyl- d -erythro-sphingosine) reduced the generation of bioactive NO (RFL-6 reporter-cell assa…
Copper(ii) and Zn(ii) coordination chemistry of tetraaza[n]cyclophanes
The acid–base behaviour and Zn2+ and Cu2+ metal coordination chemistry of the novel orthocyclophane ligands 2,5,8,11-tetraaza[12]orthocyclophane (L2) and 2,5,9,12-tetraaza[13]orthocyclophane (L3) and metacyclophane 2,5,8,11-tetraaza[12]metacylophane (L1) are studied. Important differences in the chemistry of these compounds are found depending on the substitution of the aromatic ring. The ortho derivatives are much more basic in their first two protonation steps while the metacyclophane presents much larger constants in the third and fourth protonation stages. The crystal structure of the picrate salt of [H2L3]2+ shows an alternate disposition of the protons in the molecule with formation o…