Browsing by Author "Aldunate, Rebeca"

Now showing 1 - 5 of 5
  • No Thumbnail Available
    Item
    Characterization of an Agarophyton chilense Oleoresin Containing PPARγ Natural Ligands with Insulin-Sensitizing Effects in a C57Bl/6J Mouse Model of Diet-Induced Obesity and Antioxidant Activity in Caenorhabditis elegans
    (2021) Pinto, Claudio; Raquel Ibanez, Maria; Loyola, Gloria; Leon, Luisa; Salvatore, Yasmin; Gonzalez, Carla; Barraza, Victor; Castaneda, Francisco; Aldunate, Rebeca; Contreras-Porcia, Loretto; Fuenzalida, Karen; Bronfman, Francisca C.
    The biomedical potential of the edible red seaweed Agarophyton chilense (formerly Gracilaria chilensis) has not been explored. Red seaweeds are enriched in polyunsaturated fatty acids and eicosanoids, which are known natural ligands of the PPAR gamma nuclear receptor. PPAR gamma is the molecular target of thiazolidinediones (TZDs), drugs used as insulin sensitizers to treat type 2 diabetes mellitus. Medical use of TZDs is limited due to undesired side effects, a problem that has triggered the search for selective PPAR gamma modulators (SPPARMs) without the TZD side effects. We produced Agarophyton chilense oleoresin (Gracilex(R)), which induces PPAR gamma activation without inducing adipocyte differentiation, similar to SPPARMs. In a diet-induced obesity model of male mice, we showed that treatment with Gracilex(R) improves insulin sensitivity by normalizing altered glucose and insulin parameters. Gracilex(R) is enriched in palmitic acid, arachidonic acid, oleic acid, and lipophilic antioxidants such as tocopherols and beta-carotene. Accordingly, Gracilex(R) possesses antioxidant activity in vitro and increased antioxidant capacity in vivo in Caenorhabditis elegans. These findings support the idea that Gracilex(R) represents a good source of natural PPAR gamma ligands and antioxidants with the potential to mitigate metabolic disorders. Thus, its nutraceutical value in humans warrants further investigation.
  • No Thumbnail Available
    Item
    Intracellular amyloid formation in muscle cells of Aβ-transgenic Caenorhabditis elegans: determinants and physiological role in copper detoxification
    (2009) Minniti, Alicia N.; Rebolledo, Daniela L.; Grez, Paula M.; Fadic, Ricardo; Aldunate, Rebeca; Volitakis, Irene; Cherny, Robert A.; Opazo, Carlos; Masters, Colin; Bush, Ashley I.; Inestrosa, Nibaldo C.
    Background: The amyloid beta-peptide is a ubiquitous peptide, which is prone to aggregate forming soluble toxic oligomers and insoluble less-toxic aggregates. The intrinsic and external/environmental factors that determine A beta aggregation in vivo are poorly understood, as well as the cellular meaning of this process itself. Genetic data as well as cell biological and biochemical evidence strongly support the hypothesis that A beta is a major player in the onset and development of Alzheimer's disease. In addition, it is also known that A beta is involved in Inclusion Body Myositis, a common myopathy of the elderly in which the peptide accumulates intracellularly.
  • Thumbnail Image
    Item
    Methionine sulfoxide reductase A expression is regulated by the DAF-16/FOXO pathway in Caenorhabditis elegans
    (WILEY, 2009) Minniti, Alicia N.; Cataldo, Romina; Trigo, Carla; Vasquez, Luis; Mujica, Patricio; Leighton, Federico; Inestrosa, Nibaldo C.; Aldunate, Rebeca
    P>The methionine sulfoxide reductase system has been implicated in aging and protection against oxidative stress. This conserved system reverses the oxidation of methionine residues within proteins. We analyzed one of the components of this system, the methionine sulfoxide reductase A gene, in Caenorhabditis elegans. We found that the msra-1 gene is expressed in most tissues, particularly in the intestine and the nervous system. Worms carrying a deletion of the msra-1 gene are more sensitive to oxidative stress, show chemotaxis and locomotory defects, and a 30% decrease in median survival. We established that msra-1 expression decreases during aging and is regulated by the DAF-16/FOXO3a transcription factor. The absence of this enzyme decreases median survival and affects oxidative stress resistance of long lived daf-2 worms. A similar effect of MSRA-1 absence in wild-type and daf-2 (where most antioxidant enzymes are activated) backgrounds, suggests that the lack of this member of the methionine repair system cannot be compensated by the general antioxidant response. Moreover, FOXO3a directly activates the human MsrA promoter in a cell culture system, implying that this could be a conserved mechanism of MsrA regulation. Our results suggest that repair of oxidative damage in proteins influences the rate at which tissues age. This repair mechanism, rather than the general decreased of radical oxygen species levels, could be one of the main determinants of organisms' lifespan.
  • No Thumbnail Available
    Item
    Surface enhanced fluorescence effect improves the in vivo detection of amyloid aggregates
    (2022) Cabrera, Pablo; Jara-Guajardo, Pedro; Oyarzun, Maria Paz; Parra-Munoz, Nicole; Campos, Aldo; Soler, Monica; Alvarez, Alejandra; Morales-Zavala, Francisco; Araya, Eyleen; Minniti, Alicia N.; Aldunate, Rebeca; Kogan, Marcelo J.
    The beta-amyloid (A beta) peptide is one of the key etiological agents in Alzheimer's disease (AD). The in vivo detection of A beta species is challenging in all stages of the illness. Currently, the development of fluorescent probes allows the detection of A beta in animal models in the near-infrared region (NIR). However, considering future applications in biomedicine, it is relevant to develop strategies to improve detection of amyloid aggregates using NIR probes. An innovative approach to increase the fluorescence signal of these fluorophores is the use of plasmonic gold nanoparticles (surface-enhanced fluorescence effect). In this work, we improved the detection of A beta aggregates in C. elegans and mouse models of AD by co-administering functionalized gold nanorods (GNRs-PEG-D1) with the fluorescent probes CRANAD-2 or CRANAD-58, which bind selectively to different amyloid species (soluble and insoluble). This work shows that GNRs improve the detection of A beta using NIR probes in vivo. (C) 2022 Published by Elsevier Inc.
  • Thumbnail Image
    Item
    The Protein Oxidation Repair Enzyme Methionine Sulfoxide Reductase A Modulates Aβ Aggregation and Toxicity In Vivo
    (2015) Nogueras de Minniti, Alicia Susana; Arrazola, Macarena S.; Bravo Zehnder, Marcela; Ramos, Francisca; Inestrosa Cantín, Nibaldo; Aldunate, Rebeca