Browsing by Author "Michea, Luis"

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    Dissociating angiotensin 1-9 anticardiovascular remodeling effects from those on blood pressure
    (2014) Ocaranza, María Paz; Michea, Luis; Chiong, Mariod; Lavandero, Sergio; Jalil Milad, Jorge
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    E Prostanoid-1 receptor regulates renal medullary αENaC in rats infused with angiotensin II
    (2009) Gonzalez, Alexis A.; Cespedes, Carlos; Villanueva, Sandra; Michea, Luis; Vio, Carlos P.
    E Prostanoid (EP) receptors play an important role in urinary Na+ excretion. In the kidney, the epithelial sodium channel (ENaC) is the rate-limiting-step for Na+ reabsorption. We hypothesized that activation of EP1/EP3 regulates the expression of ENaC in the face of renin-angiotensin-aldosterone-system (RAAS) activation. In primary cultures of inner medullary collecting duct (IMCD) cells, sulprostone (EP1 > EP3 agonist, 1 mu M) and 17 Phenyl trinor (17 Pt, EP1 agonist, 10 mu M) prevented the up-regulation of alpha ENaC mRNA induced by aldosterone (10 nM). In Sprague-Dawley rats infused with angiotensin II (0.4 mu g/kg/min), alpha ENaC expression was up-regulated in renal cortex and medulla coincidently with high plasma aldosterone levels. Sulprostone and/or 17 Pt prevented this effect in renal medulla but not in cortex. Immunocytochemistry demonstrated that IMCD cells express EP1. Our results suggest that specific activation of EP1 receptor during RAAS activation antagonizes the action of aldosterone on alpha ENaC expression in the renal medulla. (C) 2009 Elsevier Inc. All rights reserved.
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    Espironolactona en Hipertension Arterial Resistente
    (2013) Tagle, Rodrigo; Michea, Luis
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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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    The Ski Protein is Involved in the Transformation Pathway of Aurora Kinase A
    (WILEY, 2016) Rivas, Solange; Armisen, Ricardo; Rojas, Diego A.; Maldonado, Edio; Huerta, Hernan; Tapia, Julio C.; Espinoza, Jaime; Colombo, Alicia; Michea, Luis; Hayman, Michael J.; Marcelain, Katherine
    Oncogenic kinase Aurora A (AURKA) has been found to be overexpresed in several tumors including colorectal, breast, and hematological cancers. Overexpression of AURKA induces centrosome amplification and aneuploidy and it is related with cancer progression and poor prognosis. Here we show that AURKA phosphorylates in vitro the transcripcional co-repressor Ski on aminoacids Ser326 and Ser383. Phosphorylations on these aminoacids decreased Ski protein half-life. Reduced levels of Ski resulted in centrosomes amplification and multipolar spindles formation, same as AURKA overexpressing cells. Importantly, overexpression of Ski wild type, but not S326D and S383D mutants inhibited centrosome amplification and cellular transformation induced by AURKA. Altogether, these results suggest that the Ski protein is a target in the transformation pathway mediated by the AURKA oncogene. (C) 2015 Wiley Periodicals, Inc.