RESUMEN
The molecular mechanisms underlying the relationship between low-density lipoprotein (LDL) and the risk of atherosclerosis are not clear. Therefore, detailed information on the protein composition of LDL may help to reveal its role in atherogenesis. Liquid-phase IEF has been used to resolve LDL proteins into well-defined fractions on the basis of pI, which improves the subsequent detection and resolution of low abundance proteins. Besides known LDL-associated proteins, this approach revealed the presence of proteins not previously described to reside in LDL, including prenylcysteine lyase (PCL1), orosomucoid, retinol-binding protein, and paraoxonase-1. PCL1, an enzyme crucial for the degradation of prenylated proteins, generates free cysteine, isoprenoid aldehyde and hydrogen peroxide. Addition of the substrate farnesylcysteine to lipoprotein resulted in a time-dependent generation of H(2)O(2) which was stronger in very low density lipoprotein (VLDL) than in LDL or HDL, reflecting the greater protein content of PCL1 in VLDL. Farnesol, a dead end inhibitor of the PCL1 reaction, reduced H(2)O(2) generation by VLDL. PCL1 is generated along with nascent lipoprotein, as shown by its presence in the lipoprotein secreted by HepG2 cells. The finding that an enzyme associated with atherogenic lipoproteins can itself generate an oxidant suggests that PCL1 may play a significant role in atherogenesis.
Asunto(s)
Liasas de Carbono-Azufre/metabolismo , Peróxido de Hidrógeno/metabolismo , Lipoproteínas/análisis , Adulto , Aterosclerosis/etiología , Liasas de Carbono-Azufre/análisis , Liasas de Carbono-Azufre/antagonistas & inhibidores , Fraccionamiento Químico/métodos , Farnesol/metabolismo , Femenino , Humanos , Lipoproteínas/metabolismo , Lipoproteínas HDL/análisis , Lipoproteínas HDL/metabolismo , Lipoproteínas LDL/análisis , Lipoproteínas LDL/metabolismo , Lipoproteínas VLDL/análisis , Lipoproteínas VLDL/metabolismo , Masculino , Espectrometría de MasasRESUMEN
We observed a significant increase of Pseudomonas aeruginosa bacteremias during 2002. Eighty-five microbiological samples were taken from different potential sources of infection. Twenty-nine out of 46 specimens obtained from water taps, shower heads and siphons tested positive for Pseudomonas aeruginosa. Weekly pharyngeal and rectal swabs in high risk patients, use of tap water after running the tap for at least 5 minutes and use of weekly disposable sterile filters in all taps and showers resulted in a significant decrease in Pseudomonas aeruginosa bacteremias. Moreover, we observed a significant reduction in Pseudomonas aeruginosa-positive surveillance cultures after implementation of these measures.