Browsing by Author "Castillo, Karen"

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    BAX inhibitor-1 regulates autophagy by controlling the IRE1α branch of the unfolded protein response
    (2011) Castillo, Karen; Rojas-Rivera, Diego; Lisbona, Fernanda; Caballero, Benjamin; Nassif, Melissa; Court, Felipe A.; Schuck, Sebastian; Ibar, Consuelo; Walter, Peter; Sierralta, Jimena; Glavic, Alvaro; Hetz, Claudio
    Both autophagy and apoptosis are tightly regulated processes playing a central role in tissue homeostasis. Bax inhibitor 1 (BI-1) is a highly conserved protein with a dual role in apoptosis and endoplasmic reticulum (ER) stress signalling through the regulation of the ER stress sensor inositol requiring kinase 1 alpha (IRE1 alpha). Here, we describe a novel function of BI-1 in the modulation of autophagy. BI-1-deficient cells presented a faster and stronger induction of autophagy, increasing LC3 flux and autophagosome formation. These effects were associated with enhanced cell survival under nutrient deprivation. Repression of autophagy by BI-1 was dependent on cJun-N terminal kinase (JNK) and IRE1 alpha expression, possibly due to a displacement of TNF-receptor associated factor-2 (TRAF2) from IRE1 alpha. Targeting BI-1 expression in flies altered autophagy fluxes and salivary gland degradation. BI-1 deficiency increased flies survival under fasting conditions. Increased expression of autophagy indicators was observed in the liver and kidney of bi-1-deficient mice. In summary, we identify a novel function of BI-1 in multicellular organisms, and suggest a critical role of BI-1 as a stress integrator that modulates autophagy levels and other interconnected homeostatic processes. The EMBO Journal (2011) 30, 4465-4478. doi:10.1038/emboj.2011.318; Published online 16 September 2011
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    Maternal outcomes and risk factors for COVID-19 severity among pregnant women
    (2021) Vouga, Manon; Favre, Guillaume; Pomar, Leo; Forcen Acebal, Laura; Abascal-Saiz, Alejandra; Vila Hernandez, Maria Rosa; Hcini, Najeh; Lambert, Veronique; Carles, Gabriel; Sichitiu, Joanna; Salomon, Laurent; Stirnemann, Julien; Ville, Yves; de Tejada, Begona Martinez; Gonce, Anna; Castillo, Karen; Gratacos Solsona, Eduard; Trigo, Lucas; Cleary, Brian; Geary, Michael; Bartels, Helena; Malone, Fergal; Higgins, Mary; Keating, Niamh; Knowles, Susan; Poncelet, Christophe; Surita, Fernanda; Borrelli, Carolina; Luz, Adriana Gomes; Fuenzalida, Javiera; Carvajal, Jorge; Guerra Canales, Manuel; Hernandez, Olivia; Grechukhina, Olga; Ko, Albert, I; Reddy, Uma; Figueiredo, Rita; Moucho, Marina; Pinto, PedroViana; De Luca, Carmen; De Santis, Marco; de Campos, Diogo Ayres; Martins, Ines; Garabedian, Charles; Subtil, Damien; Bohrer, Betania; Da Rocha Oppermann, Maria Lucia; OsorioWender, Maria Celeste; Vieira Sanseverino, Maria Teresa; Giugliani, Camila; Friedrich, Luciana; Scherer, Mariana Horn; Mottet, Nicolas; Ducarme, Guillaume; Pelerin, Helene; Moreau, Chloe; Breton, Benedicte; Quibel, Thibaud; Rozenberg, Patrick; Giannoni, Eric; Granado, Cristina; Monod, Cecile; Mueller, Doris; Hoesli, Irene; Bassler, Dirk; Heldstab, Sandra; Kolble, Nicole Ochsenbein; Sentilhes, Loic; Charvet, Melissa; Deprest, Jan; Richter, Jute; Van der Veeken, Lennart; Eggel-Hort, Beatrice; Plantefeve, Gaetan; Derouich, Mohamed; Nieto Calvache, Albaro Jose; Hecher, Kurt; Hadar, Eran; Haratz, Karina Krajden; Amikam, Uri; Malinger, Gustavo; Maymon, Ron; Yogev, Yariv; Schafer, Leonhard; Toussaint, Arnaud; Rossier, Marie-Claude; De Sa, RenatoAugusto Moreira; Grawe, Claudia; Aebi-Popp, Karoline; Raio, Luigi; Surbek, Daniel; Bockenhof, Paul; Strizek, Brigitte; Kaufmann, Martin; Bloch, Andrea; Boulvain, Michel; Johann, Silke; Heldstab, SandraAndrea; Bernasconi, MonyaTodesco; Grant, Gaston; Feki, Anis; Muller Brochut, Anne-Claude; Giral, Marylene; Sedille, Lucie; Papadia, Andrea; Brugger, Romina Capoccia; Weber, Brigitte; Fischer, Tina; Kahlert, Christian; Saines, Karin Nielsen; Cambou, Mary; Kanellos, Panagiotis; Chen, Xiang; Yin, Mingzhu; Haessig, Annina; Ackermann, Sandrine; Baud, David; Panchaud, Alice
    Pregnant women may be at higher risk of severe complications associated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which may lead to obstetrical complications. We performed a case control study comparing pregnant women with severe coronavirus disease 19 (cases) to pregnant women with a milder form (controls) enrolled in the COVI-Preg international registry cohort between March 24 and July 26, 2020. Risk factors for severity, obstetrical and immediate neonatal outcomes were assessed. A total of 926 pregnant women with a positive test for SARS-CoV-2 were included, among which 92 (9.9%) presented with severe COVID-19 disease. Risk factors for severe maternal outcomes were pulmonary comorbidities [aOR 4.3, 95% CI 1.9-9.5], hypertensive disorders [aOR 2.7, 95% CI 1.0-7.0] and diabetes [aOR2.2, 95% CI 1.1-4.5]. Pregnant women with severe maternal outcomes were at higher risk of caesarean section [70.7% (n=53/75)], preterm delivery [62.7% (n=32/51)] and newborns requiring admission to the neonatal intensive care unit [41.3% (n=31/75)]. In this study, several risk factors for developing severe complications of SARS-CoV-2 infection among pregnant women were identified including pulmonary comorbidities, hypertensive disorders and diabetes. Obstetrical and neonatal outcomes appear to be influenced by the severity of maternal disease.