Browsing by Author "Criollo, Alfredo"
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- ItemFibroblast Primary Cilia Are Required for Cardiac Fibrosis(2019) Villalobos, Elisa; Criollo, Alfredo; Schiattarella, Gabriele G.; Altamirano, Francisco; French, Kristin M.; May, Herman, I; Jiang, Nan; Ngoc Uyen Nhi Nguyen; Romero, Diego; Carlos Roa, Juan; Garcia, Lorena; Diaz-Araya, Guillermo; Morselli, Eugenia; Ferdous, Anwarul; Conway, Simon J.; Sadek, Hesham A.; Gillette, Thomas G.; Lavandero, Sergio; Hill, Joseph A.BACKGROUND: The primary cilium is a singular cellular structure that extends from the surface of many cell types and plays crucial roles in vertebrate development, including that of the heart. Whereas ciliated cells have been described in developing heart, a role for primary cilia in adult heart has not been reported. This, coupled with the fact that mutations in genes coding for multiple ciliary proteins underlie polycystic kidney disease, a disorder with numerous cardiovascular manifestations, prompted us to identify cells in adult heart harboring a primary cilium and to determine whether primary cilia play a role in disease-related remodeling.
- ItemHyperosmotic stress-dependent NFκB activation is regulated by reactive oxygen species and IGF-1 in cultured cardiomyocytes(2006) Eisner, Veronica; Criollo, Alfredo; Quiroga, Clara; Olea-Azar, Claudio; Santibanez, Juan Francisco; Troncoso, Rodrigo; Chiong, Mario; Diaz-Araya, Guillermo; Foncea, Rocio; Lavandero, SergioWe have recently shown that hyperosmotic stress activates p65/RelB NF kappa B in cultured cardiomyocytes with dichotomic actions on caspase activation and cell death. It remains unexplored how NFKB is regulated in cultured rat cardiomyocytes exposed to hyperosmotic stress. We study here: (a) if hyperosmotic stress triggers reactive oxygen species (ROS) generation and in turn whether they regulate NFKB and (b) if insulin-like growth factor-1 (IGF-1) modulates ROS production and NF kappa B activation in hyperosmotically-stressed cardiomyocytes. The results showed that hyperosmotic stress generated ROS in cultured cardiac myocytes, in particular the hydroxyl and superoxide species, which were inhibited by N-acetylcysteine (NAC). Hyperosmotic stress-induced NFKB activation as determined by I kappa B alpha degradation and NF kappa B DNA binding. NFKB activation and procaspase-3 and -9 fragmentation were prevented by NAC and IGF-1. However, this growth factor did not decrease ROS generation induced by hyperosmotic stress, suggesting that its actions over NFKB and caspase activation may be due to modulation of events downstream of ROS generation. We conclude that hyperosmotic stress induces ROS, which in turn activates NF kappa B and caspases. IGF-1 prevents NFKB activation by a ROS-independent mechanism. (c) 2006 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
- ItemImpact of estrogens and estrogen receptor-a in brain lipid metabolism(2018) Morselli, Eugenia; de Souza Santos, Roberta; Gao, Su; Ávalos, Yenniffer; Criollo, Alfredo; Palmer, Biff F.; Clegg, Deborah J.
- ItemInhibition of PORCN Blocks Wnt Signaling to Attenuate Progression of Oral Carcinogenesis(2024) Pena-Oyarzun, Daniel; Flores, Tania; Torres, Vicente A.; Quest, Andrew F. G.; Lobos-Gonzalez, Lorena; Kretschmar, Catalina; Contreras, Pamela; Maturana-Ramirez, Andrea; Criollo, Alfredo; Reyes, MontserratPurpose: Oral squamous cell carcinoma (OSCC) is commonly preceded by potentially malignant lesions, referred to as oral dysplasia. We recently reported that oral dysplasia is associated with aberrant activation of the Wnt/beta-catenin pathway, due to overexpression of Wnt ligands in a Porcupine (PORCN)-dependent manner. Pharmacologic inhibition of PORCN precludes Wnt secretion and has been proposed as a potential therapeutic approach to treat established cancers. Nevertheless, there are no studies that explore the effects of PORCN inhibition at the different stages of oral carcinogenesis.
- ItemPalmitic acid control of ciliogenesis modulates insulin signaling in hypothalamic neurons through an autophagy-dependent mechanism(SPRINGERNATURE, 2022) Avalos, Yenniffer; Paz Hernandez-Caceres, Maria; Lagos, Pablo; Pinto-Nunez, Daniela; Rivera, Patricia; Burgos, Paulina; Diaz-Castro, Francisco; Joy-Immediato, Michelle; Venegas-Zamora, Leslye; Lopez-Gallardo, Erik; Kretschmar, Catalina; Batista-Gonzalez, Ana; Cifuentes-Araneda, Flavia; Toledo-Valenzuela, Lilian; Rodriguez-Pena, Marcelo; Espinoza-Caicedo, Jasson; Perez-Leighton, Claudio; Bertocchi, Cristina; Cerda, Mauricio; Troncoso, Rodrigo; Parra, Valentina; Budini, Mauricio; Burgos, Patricia, V; Criollo, Alfredo; Morselli, EugeniaPalmitic acid (PA) is significantly increased in the hypothalamus of mice, when fed chronically with a high-fat diet (HFD). PA impairs insulin signaling in hypothalamic neurons, by a mechanism dependent on autophagy, a process of lysosomal-mediated degradation of cytoplasmic material. In addition, previous work shows a crosstalk between autophagy and the primary cilium (hereafter cilium), an antenna-like structure on the cell surface that acts as a signaling platform for the cell. Ciliopathies, human diseases characterized by cilia dysfunction, manifest, type 2 diabetes, among other features, suggesting a role of the cilium in insulin signaling. Cilium depletion in hypothalamic pro-opiomelanocortin (POMC) neurons triggers obesity and insulin resistance in mice, the same phenotype as mice deficient in autophagy in POMC neurons. Here we investigated the effect of chronic consumption of HFD on cilia; and our results indicate that chronic feeding with HFD reduces the percentage of cilia in hypothalamic POMC neurons. This effect may be due to an increased amount of PA, as treatment with this saturated fatty acid in vitro reduces the percentage of ciliated cells and cilia length in hypothalamic neurons. Importantly, the same effect of cilia depletion was obtained following chemical and genetic inhibition of autophagy, indicating autophagy is required for ciliogenesis. We further demonstrate a role for the cilium in insulin sensitivity, as cilium loss in hypothalamic neuronal cells disrupts insulin signaling and insulin-dependent glucose uptake, an effect that correlates with the ciliary localization of the insulin receptor (IR). Consistently, increased percentage of ciliated hypothalamic neuronal cells promotes insulin signaling, even when cells are exposed to PA. Altogether, our results indicate that, in hypothalamic neurons, impairment of autophagy, either by PA exposure, chemical or genetic manipulation, cause cilia loss that impairs insulin sensitivity.
- ItemPalmitic and Stearic Acids Inhibit Chaperone-Mediated Autophagy (CMA) in POMC-like Neurons In Vitro(2022) Espinosa, Rodrigo; Gutierrez, Karla; Rios, Javiera; Ormeno, Fernando; Yanten, Liliana; Galaz-Davison, Pablo; Ramirez-Sarmiento, Cesar A.; Parra, Valentina; Albornoz, Amelina; Alfaro, Ivan E.; Burgos, Patricia, V; Morselli, Eugenia; Criollo, Alfredo; Budini, MauricioThe intake of food with high levels of saturated fatty acids (SatFAs) is associated with the development of obesity and insulin resistance. SatFAs, such as palmitic (PA) and stearic (SA) acids, have been shown to accumulate in the hypothalamus, causing several pathological consequences. Autophagy is a lysosomal-degrading pathway that can be divided into macroautophagy, microautophagy, and chaperone-mediated autophagy (CMA). Previous studies showed that PA impairs macroautophagy function and insulin response in hypothalamic proopiomelanocortin (POMC) neurons. Here, we show in vitro that the exposure of POMC neurons to PA or SA also inhibits CMA, possibly by decreasing the total and lysosomal LAMP2A protein levels. Proteomics of lysosomes from PA- and SA-treated cells showed that the inhibition of CMA could impact vesicle formation and trafficking, mitochondrial components, and insulin response, among others. Finally, we show that CMA activity is important for regulating the insulin response in POMC hypothalamic neurons. These in vitro results demonstrate that CMA is inhibited by PA and SA in POMC-like neurons, giving an overview of the CMA-dependent cellular pathways that could be affected by such inhibition and opening a door for in vivo studies of CMA in the context of the hypothalamus and obesity.
- ItemPolycystin-2 Is Required for Starvation- and Rapamycin-Induced Atrophy in Myotubes(2019) Kretschmar, Catalina; Pena-Oyarzun, Daniel; Hernando, Cecilia; Hernandez-Moya, Nadia; Molina-Berrios, Alfredo; Paz Hernandez-Caceres, Maria; Lavandero, Sergio; Budini, Mauricio; Morselli, Eugenia; Parra, Valentina; Troncoso, Rodrigo; Criollo, AlfredoMuscle atrophy involves a massive catabolism of intracellular components leading to a significant reduction in cellular and tissue volume. In this regard, autophagy, an intracellular mechanism that degrades proteins and organelles, has been implicated with muscle breakdown. Recently, it has shown that polycystin-2 (PC2), a membrane protein that belongs to the transient receptor potential (TRP) family, is required for the maintenance of cellular proteostasis, by regulating autophagy in several cell types. The role of PC2 in the control of atrophy and autophagy in skeletal muscle remains unknown. Here, we show that PC2 is required for the induction of atrophy in C2C12 myotubes caused by nutrient deprivation or rapamycin exposure. Consistently, overexpression of PC2 induces atrophy in C2C12 myotubes as indicated by decreasing of the myogenic proteins myogenin and caveolin-3. In addition, we show that inhibition of mTORC1, by starvation or rapamycin is inhibited in cells when PC2 is silenced. Importantly, even if PC2 regulates mTORC1, our results show that the regulation of atrophy by PC2 is independent of autophagy. This study provides novel evidence regarding the role of PC2 in skeletal muscle cell atrophy.
- ItemRegulation of cardiomyocyte autophagy by calcium(2016) Shaikh, Soni; Troncoso, Rodrigo; Criollo, Alfredo; Bravo Sagua, Roberto; García, Lorena; Morselli, Eugenia; Cifuentes, Mariana; Quest, Andrew F. G.; Hill, Joseph A.; Lavandero, Sergio
- ItemSex Hormones and Cardiometabolic Health: Role of Estrogen and Estrogen Receptors(2017) Clegg, Deborah; Hevener, Andrea L.; Moreau, Kerrie L.; Morselli, Eugenia; Criollo, Alfredo; Van Pelt, Rachael E.; Vieira Potter, Victoria J.
- ItemThe effects of oestrogens and their receptors on cardiometabolic health(2017) Morselli, Eugenia; Santos, Roberta S.; Criollo, Alfredo; Nelson, Michael D.; Palmer, Biff F.; Clegg, Deborah J.