Browsing by Author "Fuenzalida, Karen"

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    Hepatic fatty acid profile in mice with nonalcoholic fatty liver disease using magnetic resonance spectroscopy
    (2019) Xavier, Aline Carvalho da Silva; Zacconi, Flavia C. M.; Cabrera García, Daniel Alejandro; Fuenzalida, Karen; Andía Kohnenkampf, Marcelo Edgardo
    Nonalcoholic fatty liver disease (NAFLD) is characterized by the accumulation of intracellular fatty acids in the liver. The only method to confirm the stage of this disease is the biopsy, but it is invasive and risky to patients. The idea of defining a classifier using magnetic resonance spectroscopy (MRS) emerges due to the need to find a way to replace biopsy with a non-invasive method that can classify NAFLD based on the chemical structure of fatty acids stored in the liver. The purpose of this study is to investigate and compare the composition of fatty acids to the metabolites signals in MRS in NAFLD mice liver at 2 time-point during the progression of the disease. A group of C57BL/6 mice was fed with high-fat diet for one month (N = 8) and for three months (N = 6). First, we made a histological analysis to the liver. Then, we analysed the fatty acids with gas chromatography (GC) and MRS. As a result, the histological analysis showed the progression of fat content, and the GC analysis detected a different fatty acid liver composition during the progression of NAFLD along with an increase of the total fat storage in the liver. The differences in the composition fatty acids are also reflected in the MR Spectrum, which could have clinical potential for monitoring the progression of this disease with a non-invasive technique.
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    Peroxisome proliferator-activated receptor gamma up-regulates the Bcl-2 anti-apoptotic protein in neurons and induces mitochondrial stabilization and protection against oxidative stress and apoptosis
    (AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 2007) Fuenzalida, Karen; Quintanilla, Rodrigo; Ramos, Patricio; Piderit, Daniela; Fuentealba, Rodrigo A.; Martinez, Gabriela; Inestrosa, Nibaldo C.; Bronfman, Miguel
    Peroxisome proliferator-activated receptor gamma(PPAR gamma) has been proposed as a therapeutic target for neurodegenerative diseases because of its anti-inflammatory action in glial cells. However, PPAR gamma agonists prevent beta-amyloid (A beta)-induced neurodegeneration in hippocampal neurons, and PPAR gamma is activated by the nerve growth factor (NGF) survival pathway, suggesting a neuroprotective anti-inflammatory independent action. Here we show that the PPAR gamma agonist rosiglitazone (RGZ) protects hippocampal and dorsal root ganglion neurons against A beta-induced mitochondrial damage and NGF deprivation-induced apoptosis, respectively, and promotes PC12 cell survival. In neurons and in PC12 cells RGZ protective effects are associated with increased expression of the Bcl-2 anti-apoptotic protein. NGF-differentiated PC12 neuronal cells constitutively overexpressing PPAR gamma are resistant to A beta-induced apoptosis and morphological changes and show functionally intact mitochondria and no increase in reactive oxygen species when challenged with up to 50 mu M H2O2. Conversely, cells expressing a dominant negative mutant of PPAR gamma show increased A beta-induced apoptosis and disruption of neuronal-like morphology and are highly sensitive to oxidative stress-induced impairment of mitochondrial function. Cells overexpressing PPAR gamma present a 4-to 5-fold increase in Bcl-2 protein content, whereas in dominant negative PPAR gamma-expressing cells, Bcl-2 is barely detected. Bcl-2 knockdown by small interfering RNA in cells overexpressing PPAR gamma results in increased sensitivity to A beta and oxidative stress, further suggesting that Bcl-2 up-regulation mediates PPAR gamma protective effects. PPAR gamma prosurvival action is independent of the signal-regulated MAPK or the Akt prosurvival pathways. Altogether, these data suggest that PPAR gamma supports survival in neurons in part through a mechanism involving increased expression of Bcl-2.