Browsing by Author "Lagos Arévalo, Carlos Fernando"

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    1-benzoyl-2-(2-nitrophenyl)-1H-benzimidazole derivatives: A novel approach to the development of new HIV-1 reverse transcriptase inhibitors
    (2007) Vásquez Velásquez, David; Lagos Arévalo, Carlos Fernando; Mella Raipán, Jaime Alberto; González Contreras, Luis Gerardo; Ebensperger González, Roberto Alejandro; Alvarez Figueroa, María Javiera; Sáez Moya, Edmundo Alfredo; Pessoa Mahana, Hernán; Araya Secchi, Raul; Gonzalez Wong, Angel; Perez-Acle, Tomas; Pessoa Mahana, Carlos David
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    A new presentation of the chimeric CYP11B1/CYP11B2 gene with low prevalence of primary aldosteronism and atypical gene segregation pattern
    (Lippincott Williams & Wilkins, 2012) Carvajal Maldonado, Cristian Andrés; Campino Johnson, María del Carmen; Martínez Aguayo, Alejandro Gregorio; Tichauer Calderón, Juan Enrique; Bancalari, Rodrigo; Valdivia, Carolina; Trejo, Pamela; Aglony Imbarack, Marlene Elizabeth; Baudrand Biggs, René Felipe; Lagos Arévalo, Carlos Fernando; Mellado Sagredo, Cecilia Ximena Del Carmen; García Bruce, Hernán Gabriel; Fardella Bello, Carlos Enrique
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    A recurrent p.Arg92Trp variant in steroidogenic factor-1 (NR5A1) can act as a molecular switch in human sex development
    (2016) Bashamboo, Anu; Donohoue, Patricia A.; Vilain, Eric; Rojo, Sandra; Lagos Arévalo, Carlos Fernando
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    An Amphipathic Alpha-Helix in the Prodomain of Cocaine and Amphetamine Regulated Transcript Peptide Precursor Serves as Its Sorting Signal to the Regulated Secretory Pathway
    (2013) Blanco Nahuelqueo, Elías; Lagos Arévalo, Carlos Fernando; Andrés Coke, María Estela; Gysling Caselli, Katia
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    APOA5 Q97X Mutation Identified through homozygosity mapping causes severe hypertriglyceridemia in a Chilean consanguineous family
    (2012) Dussaillant, Catalina; Serrano Larrea, Valentina; Maiz Gurruchaga, Manuel Alberto; Eyheramendy Duerr, Susana; Cataldo Bascuñan, Luis Rodrigo; Smalley Meylan, Susan Valerie; Rigotti Rivera, Attilio; Rubio, Lorena.; Lagos Arévalo, Carlos Fernando; Santos Martín, José Luis
    Abstract Background Severe hypertriglyceridemia (HTG) has been linked to defects in LPL, APOC2, APOA5, LMF1 and GBIHBP1 genes. However, a number of severe HTG cases are probably caused by as yet unidentified mutations. Very high triglyceride plasma levels (>112 mmol/L at diagnosis) were found in two sisters of a Chilean consanguineous family, which is strongly suggestive of a recessive highly penetrant mutation. The aim of this study was to determine the genetic locus responsible for the severe HTG in this family. Methods We carried out a genome-wide linkage study with nearly 300,000 biallelic markers (Illumina Human CytoSNP-12 panel). Using the homozygosity mapping strategy, we searched for chromosome regions with excess of homozygous genotypes in the affected cases compared to non-affected relatives. Results A large homozygous segment was found in the long arm of chromosome 11, with more than 2,500 consecutive homozygous SNP shared by the proband with her affected sister, and containing the APOA5/A4/C3/A1 cluster. Direct sequencing of the APOA5 gene revealed a known homozygous nonsense Q97X mutation (p.Gln97Ter) found in both affected sisters but not in non-affected relatives nor in a sample of unrelated controls. Conclusion The Q97X mutation of the APOA5 gene in homozygous status is responsible for the severe hypertriglyceridemia in this family. We have shown that homozygosity mapping correctly pinpointed the genomic region containing the gene responsible for severe hypertriglyceridemia in this consanguineous Chilean family.
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    Basolateral sorting of chloride channel 2 is mediated by interactions between a dileucine motif and the clathrin adaptor AP-1
    (2015) de la Fuente-Ortega, Erwin; Gravotta, Diego; Perez Bay, Andres; Benedicto, Ignacio; Carvajal-Gonzalez, Jose Maria; Lehmann, Guillermo L.; Lagos Arévalo, Carlos Fernando; Rodríguez-Boulan, Enrique
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    Clinical, Biochemical, and Genetic Characteristics of "Nonclassic" Apparent Mineralocorticoid Excess Syndrome
    (2019) Tapia Castillo, Alejandra; Baudrand Biggs, René; Vaidya, Anand; Campino Johnson, María del Carmen; Allende, Fidel; Carvajal Maldonado, Cristián Andrés; Vecchiola Cárdenas, Andrea Paola; Lagos Arévalo, Carlos Fernando; Fuentes Zúñiga, Cristóbal Andrés; Fardella B., Carlos; Solari, Sandra; Martínez Aguayo, Alejandro Gregorio; García Bruce, Hernán; Valdivia, Carolina; Tapia Castillo, Alejandra; Baudrand Biggs, René; Vaidya, Anand; Campino Johnson, María del Carmen; Allende, Fidel; Carvajal Maldonado, Cristián Andrés; Vecchiola Cárdenas, Andrea Paola; Lagos Arévalo, Carlos Fernando; Fuentes Zúñiga, Cristóbal Andrés; Fardella B., Carlos; Solari, Sandra; Martínez Aguayo, Alejandro Gregorio; García Bruce, Hernán; Valdivia, Carolina
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    Computational modeling study of functional microdomains in cannabinoid receptor type 1
    (2008) González Wong, Ángel; Pessoa Mahana, Carlos David; Lagos Arévalo, Carlos Fernando; Pérez-Acle, Tomás
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    Dictyostelium discoideum as a surrogate host-microbe model for antivirulence screening in Pseudomonas aeruginosa PAO1
    (2016) Bravo Toncio, Catalina; Alvarez, Javiera A.; Campos, Francisca; Ortiz Severin, Javiera; Varas, Macarena; Cabrera, Ricardo; Lagos Arévalo, Carlos Fernando; Chávez, Francisco P.
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    Different effects of progesterone and estradiol on chimeric and wild type aldosterone synthase in vitro
    (2013) Vecchiola Cárdenas, Andrea Paola; Lagos Arévalo, Carlos Fernando; Fuentes Zúñiga, Cristóbal Andrés; Allende, Fidel; Campino Johnson, María del Carmen; Valdivia, Carolina.; Tapia Castillo, Alejandra.; Owen, Gareth Ivor; Solari Gajardo, Sandra; Carvajal Maldonado, Cristián Andrés; Fardella B., Carlos; Ogishima, Tadashi.; Mukai, Kuniaki.
    Abstract Background Familial hyperaldosteronism type I (FH-I) is caused by the unequal recombination between the 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes, resulting in the generation of a CYP11B1/B2 chimeric gene and abnormal adrenal aldosterone production. Affected patients usually show severe hypertension and an elevated frequency of stroke at a young age. Aldosterone levels rise during pregnancy, yet in pregnant women with FH-1, their hypertensive condition either remains unchanged or may even improve. The purpose of this study was to investigate in vitro whether female sex steroids modulate the activity of chimeric (ASCE) or wild type (ASWT) aldosterone synthase enzymes. Methods We designed an in vitro assay using HEK-293 cell line transiently transfected with vectors containing the full ASCE or ASWT cDNAs. Progesterone or estradiol effects on AS enzyme activities were evaluated in transfected cells incubated with deoxycorticosterone (DOC) alone or DOC plus increasing doses of these steroids. Results In our in vitro model, both enzymes showed similar apparent kinetic parameters (Km = 1.191 microM and Vmax = 27.08 microM/24 h for ASCE and Km = 1.163 microM and Vmax = 36.98 microM/24 h for ASWT; p = ns, Mann–Whitney test). Progesterone inhibited aldosterone production by ASCE- and ASWT-transfected cells, while estradiol demonstrated no effect. Progesterone acted as a competitive inhibitor for both enzymes. Molecular modelling studies and binding affinity estimations indicate that progesterone might bind to the substrate site in both ASCE and ASWT, supporting the idea that this steroid could regulate these enzymatic activities and contribute to the decay of aldosterone synthase activity in chimeric gene-positive patients. Conclusions Our results show an inhibitory action of progesterone in the aldosterone synthesis by chimeric or wild type aldosterone synthase enzymes. This is a novel regulatory mechanism of progesterone action, which could be involved in protecting pregnant women with FH-1 against hypertension. In vitro, both enzymes showed comparable kinetic parameters, but ASWT was more strongly inhibited than ASCE. This study implicates a new role for progesterone in the regulation of aldosterone levels that could contribute, along with other factors, to the maintenance of an adequate aldosterone-progesterone balance in pregnancy.Abstract Background Familial hyperaldosteronism type I (FH-I) is caused by the unequal recombination between the 11beta-hydroxylase (CYP11B1) and aldosterone synthase (CYP11B2) genes, resulting in the generation of a CYP11B1/B2 chimeric gene and abnormal adrenal aldosterone production. Affected patients usually show severe hypertension and an elevated frequency of stroke at a young age. Aldosterone levels rise during pregnancy, yet in pregnant women with FH-1, their hypertensive condition either remains unchanged or may even improve. The purpose of this study was to investigate in vitro whether female sex steroids modulate the activity of chimeric (ASCE) or wild type (ASWT) aldosterone synthase enzymes. Methods We designed an in vitro assay using HEK-293 cell line transiently transfected with vectors containing the full ASCE or ASWT cDNAs. Progesterone or estradiol effects on AS enzyme activities were evaluated in transfected cells incubated with deoxycorticosterone (DOC) alone or DOC plus increasing doses of these steroids. Results In our in vitro model, both enzymes showed similar apparent kinetic parameters (Km = 1.191 microM and Vmax = 27.08 microM/24 h for ASCE and Km = 1.163 microM and Vmax = 36.98 microM/24 h for ASWT; p = ns, Mann–Whitney test). Progesterone inhibited aldosterone production by ASCE- and ASWT-transfected cells, while estradiol demonstrated no effect. Progesterone acted as a competitive inhibitor for both enzymes. Molecular modelling studies and binding affinity estimations indicate that progesterone might bind to the substrate site in both ASCE and ASWT, supporting the idea that this steroid could regulate these enzymatic activities and contribute to the decay of aldosterone synthase activity in chimeric gene-positive patients. Conclusions Our results show an inhibitory action of progesterone in the aldosterone synthesis by chimeric or wild type aldosterone synthase enzymes. This is a novel regulatory mechanism of progesterone action, which could be involved in protecting pregnant women with FH-1 against hypertension. In vitro, both enzymes showed comparable kinetic parameters, but ASWT was more strongly inhibited than ASCE. This study implicates a new role for progesterone in the regulation of aldosterone levels that could contribute, along with other factors, to the maintenance of an adequate aldosterone-progesterone balance in pregnancy.
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    Identification of novel 11β-HSD1 inhibitors by combined ligand- and structure-based virtual screening
    (2014) Lagos Arévalo, Carlos Fernando; Vecchiola Cárdenas, Andrea Paola; Allende, Fidel; Fuentes Zúñiga, Cristóbal Andrés; Tichauer, Juan E.; Valdivia, Carolina; Solari Gajardo, Sandra; Campino Johnson, María del Carmen; Tapia-Castillo, Alejandra; Baudrand Biggs, René; Villarroel, Pia; Cifuentes, Mariana; Owen, Gareth Ivor; Carvajal, Cristian A.; Fardella B., Carlos
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    Late-onset X-linked adrenal hypoplasia (DAX-1, NR0B1): two new adult-onset cases from a single center
    (2017) Kyriakakis, Nikolaos; Shonibare, Tolulope; Kyaw-Tun, Julie; Lynch, Julie; Lagos Arévalo, Carlos Fernando; Achermann, John C.; Murray, Robert D.4
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    LC-MS/MS Method for the Simultaneous Determination of Free Urinary Steroids
    (2014) Allende, Fidel; Solari Gajardo, Sandra; Campino Johnson, María del Carmen; Carvajal Maldonado, Cristián Andrés; Lagos Arévalo, Carlos Fernando; Vecchiola Cárdenas, Andrea Paola; Baudrand Biggs, René; Owen, Gareth Ivor; Fardella B., Carlos
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    Molecular modeling of structures and interaction of human corticotropin-releasing factor (CRF) binding protein and CRF Type-2 receptor
    (2018) Slater Guzmán, Paula Gabriela; Gutierrez-Maldonado, Sebastian; Gysling Caselli, Katia; Lagos Arévalo, Carlos Fernando
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    Recent insights and therapeutic perspectives of angiotensin-(1-9) in the cardiovascular system
    (2014) Ocaranza Jeraldino, María Paz; Michea, Luis; Chiong, Mario; Lagos Arévalo, Carlos Fernando; Lavandero, Sergio; Jalil Milad, Jorge Emilio
    Chronic RAS (renin-angiotensin system) activation by both AngII (angiotensin II) and aldosterone leads to hypertension and perpetuates a cascade of pro-hypertrophic, pro-inflammatory, pro-thrombotic and atherogenic effects associated with cardiovascular damage. In 2000, a new pathway consisting of ACE2 (angiotensin-converting enzyme2), Ang-(1-9) [angiotensin-(1-9)], Ang-(1-7) [angiotensin-(1-7)] and the Mas receptor was discovered. Activation of this novel pathway stimulates vasodilation, anti-hypertrophy and anti-hyperplasia. For some time, studies have focused mainly on ACE2, Ang-(1-7) and the Mas receptor, and their biological properties that counterbalance the ACE/AngII/AT(1)R (angiotensin type 1 receptor) axis. No previous information about Ang-(1-9) suggested that this peptide had biological properties. However, recent data suggest that Ang-(1-9) protects the heart and blood vessels (and possibly the kidney) from adverse cardiovascular remodelling in patients with hypertension and/or heart failure. These beneficial effects are not modified by the Mas receptor antagonist A779 [an Ang-(1-7) receptor blocker], but they are abolished by-the AT(2)R (angiotensin type 2 receptor) antagonist PD123319. Current information suggests that the beneficial effects of Ang-(1-9) are mediated via the AT2R. In the present review, we summarize the biological effects of the novel vasoactive peptide Ang-(1-9), providing new evidence of its cardiovascular-protective activity. We also discuss the potential mechanism by which this peptide prevents and ameliorates the cardiovascular damage induced by RAS activation.
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    Serum cortisol and cortisone as potential biomarkers of partial 11β-hydroxysteroid dehydrogenase type 2 deficiency
    (2018) Carvajal Maldonado, Cristián Andrés; Tapia Castillo, Alejandra; Valdivia, Carolina P.; Allende, Fidel; Solari Gajardo, Sandra; Lagos Arévalo, Carlos Fernando; Campino Johnson, María del Carmen; Martínez Aguayo, Alejandro Gregorio; Vecchiola Cárdenas, Andrea Paola; Pinochet, Constanza