Browsing by Author "González, M"

Now showing 1 - 3 of 3
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    Cell signalling-mediating insulin increase of mRNA expression for cationic amino acid transporters-1 and-2 and membrane hyperpolarization in human umbilical vein endothelial cells
    (2004) González, M; Flores, C; Pearson, JD; Casanello, P; Sobrevia, L
    Insulin induces vasodilatation in human subjects and increases L-arginine transport and NO synthesis in human umbilical vein endothelial cells (HUVEC). Cell signalling events associated with insulin effects on activity and mRNA expression of the human cationic amino acid transporters 1 (hCAT-1) and 2B (hCAT-2B) are unknown. L-Arginine transport and eNOS activity were determined in HUVEC exposed to insulin. mRNA levels for hCAT-1, hCAT-2B and eNOS were quantitated by real time RTPCR and endothelial NO synthase (eNOS) protein was identified by Western blot analysis. Intracellular Ca2+, L-arginine and L-citrulline levels, L-[H-3]citrulline formation from L-[H-3]arginine, cGMP formation, nitrite level, ATP release and membrane potential were determined. Insulin increased L-arginine transport and the mRNA levels for hCAT-1 and hCAT-2B and eNOS expression and activity. Insulin also induced membrane hyperpolarization and increased intracellular Ca2+, L-[H-3]citrulline, cGMP and nitrite formation. Insulin-mediated stimulation of the L-arginine/NO pathway is thus associated with increased hCAT-1 and hCAT-2B mRNA, and eNOS expression, via mechanisms involving membrane hyperpolarization, mitogen-activated protein kinases p42 and p44, phosphatidylinositol 3-kinase, NO and protein kinase C. We have characterized a cell signalling pathway by which hyper-insulinaemia could lead to vasodilatation in human subjects, and which could have implications in patients in whom plasma insulin levels are altered, such as in diabetes mellitus.
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    Delirium
    (2005) González, M; de Pablo, J; Valdés, M; Matrai, S; Peri, JM; Fuente, E
    The frequency of delirium in elderly inpatients is high, resulting in poor hospital outcomes. The objective of this study is to assess whether delirium is an independent predictor for mortality over a three-month period.
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    The N-terminal copper-binding domain of the amyloid precursor protein protects against Cu2+ neurotoxicity in vivo
    (2004) Cerpa, WF; Barría, MI; Chacón, MA; Suazo, M; González, M; Opazo, C; Bush, AI; Inestrosa, NC
    The amyloid precursor protein (APP) contains a Cu binding domain (CuBD) localized between amino acids 135 and 156 (APP(135-156)), which can reduce Cu2+ to Cu1+ in vitro. The physiological function of this APP domain has not yet being established; nevertheless several studies support the notion that the CuBD of APP is involved in Cu homeostasis. We used APP synthetic peptides to evaluate their protective properties against Cu2+ neurotoxicity in a bilateral intra-hippocampal injection model. We found that human APP135-156 protects against Cu2+-induced neurotoxic effects, such as, impairment of spatial memory, neuronal cell loss, and astrogliosis. APP135-156 lacking two histidine residues showed protection against Cu2+; however, APP135-156 mutated in cysteine 144, a key residue in the reduction of Cu2+ to Cu1+, did not protect against Cu2+ neurotoxicity. In accordance with recent reports, the CuBD of the Caenorhabditis elegans, APL-1 protected against Cu2+ neurotoxicity in vivo. We also found that Cu2+ neurotoxicity is associated with an increase in nitrotyrosine immunofluorescence as well as with a decrease in Cu2+ uptake. The CuBD of APP therefore may play a role in the detoxification of brain Cu.