RETAMAL LUCERO, MAURICIO ANTONIO
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RETAMAL LUCERO, MAURICIO ANTONIO
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mretamal@udd.cl
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Scopus Author ID
8502472600

Research Output

2024 2024 2023 2023 2022 2022 2021 2021 2020 2020 2019 2019 2018 2018 2017 2017 2016 2016 2015 2015 0 0 2 2 4 4 6 6 8 8 10 10
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Ototoxicity induced by platinum-based chemotherapy

2022 , Cortés Fuentes , I.A., Hospital Barros Luco-Trudeau , University of Washington , RETAMAL LUCERO, MAURICIO ANTONIO

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Remembrances of Dr. Michael V.L. Bennett by Iberoamerican Colleagues and Friends

2024 , Verónica Abudara , Ricardo C. Araneda , Luis Barrio , Viviana M. Berthoud , Jorge E. Contreras , Eliseo Eugenín , Juan Lerma , Juan A. Orellana , Nicolás Palacios-Prado , Elia Martha Pérez-Armendariz , RETAMAL LUCERO, MAURICIO ANTONIO , Juan C. Sáez

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4-Hydroxynonenal induces Cx46 hemichannel inhibition through its carbonylation

2020 , Mauricio A. Retamal , Mariana C. Fiori , Ainoa Fernandez-Olivares , Sergio Linsambarth , Francisca Peña , Daisy Quintana , Jimmy Stehberg , Guillermo A. Altenberg

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Release of gliotransmitters through astroglial connexin 43 hemichannels is necessary for fear memory consolidation in the basolateral amygdala

2012 , Jimmy Stehberg , Rodrigo Moraga‐Amaro , Christian Salazar , Alvaro Becerra , Cesar Echeverría , Juan A. Orellana , Geert Bultynck , Raf Ponsaerts , Luc Leybaert , Felipe Simon , Juan C. Sáez , Mauricio A. Retamal

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Cardiac remodeling and arrhythmogenesis are ameliorated by administration of Cx43 mimetic peptide Gap27 in heart failure rats

2020 , Claudia M. Lucero , David C. Andrade , Camilo Toledo , Hugo S. Díaz , Katherin V. Pereyra , Esteban Diaz-Jara , Karla G. Schwarz , Noah J. Marcus , RETAMAL LUCERO, MAURICIO ANTONIO , Rodrigo A. Quintanilla , Rodrigo Del Rio

AbstractAlterations in connexins and specifically in 43 isoform (Cx43) in the heart have been associated with a high incidence of arrhythmogenesis and sudden death in several cardiac diseases. We propose to determine salutary effect of Cx43 mimetic peptide Gap27 in the progression of heart failure. High-output heart failure was induced by volume overload using the arterio-venous fistula model (AV-Shunt) in adult male rats. Four weeks after AV-Shunt surgery, the Cx43 mimetic peptide Gap27 or scrambled peptide, were administered via osmotic minipumps (AV-ShuntGap27 or AV-ShuntScr) for 4 weeks. Cardiac volumes, arrhythmias, function and remodeling were determined at 8 weeks after AV-Shunt surgeries. At 8th week, AV-ShuntGap27 showed a marked decrease in the progression of cardiac deterioration and showed a significant improvement in cardiac functions measured by intraventricular pressure-volume loops. Furthermore, AV-ShuntGap27 showed less cardiac arrhythmogenesis and cardiac hypertrophy index compared to AV-ShuntScr. Gap27 treatment results in no change Cx43 expression in the heart of AV-Shunt rats. Our results strongly suggest that Cx43 play a pivotal role in the progression of cardiac dysfunction and arrhythmogenesis in high-output heart failure; furthermore, support the use of Cx43 mimetic peptide Gap27 as an effective therapeutic tool to reduce the progression of cardiac dysfunction in high-output heart failure.

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ATP Is Required and Advances Cytokine-Induced Gap Junction Formation in Microglia In Vitro

2013 , Pablo J. Sáez , Kenji F. Shoji , RETAMAL LUCERO, MAURICIO ANTONIO , Paloma A. Harcha , Gigliola Ramírez , Jean X. Jiang , Rommy von Bernhardi , Juan C. Sáez

Microglia are the immune cells in the central nervous system. After injury microglia release bioactive molecules, including cytokines and ATP, which modify the functional state of hemichannels (HCs) and gap junction channels (GJCs), affecting the intercellular communication via extracellular and intracellular compartments, respectively. Here, we studied the role of extracellular ATP and several cytokines as modulators of the functional state of microglial HCs and GJCs using dye uptake and dye coupling techniques, respectively. In microglia and the microglia cell line EOC20, ATP advanced the TNF-α/IFN-γ-induced dye coupling, probably through the induction of IL-1βrelease. Moreover, TNF-α/IFN-γ, but not TNF-αplus ATP, increased dye uptake in EOC20 cells. Blockade of Cx43 and Panx1 HCs prevented dye coupling induced by TNF-α/IFN-γ, but not TNF-αplus ATP. In addition, IL-6 prevented the induction of dye coupling and HC activity induced by TNF-α/IFN-γin EOC20 cells. Our data support the notion that extracellular ATP affects the cellular communication between microglia through autocrine and paracrine mechanisms, which might affect the timing of immune response under neuroinflammatory conditions.

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Regulation of Connexin-Based Channels by Fatty Acids

2017 , Carlos Puebla , RETAMAL LUCERO, MAURICIO ANTONIO , ACUÑA ASTUDILLO, RODRIGO ANTONIO , Juan C. Sáez

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Connexin46 Expression Enhances Cancer Stem Cell and Epithelial-to-Mesenchymal Transition Characteristics of Human Breast Cancer MCF-7 Cells

2021 , ACUÑA ASTUDILLO, RODRIGO ANTONIO , Manuel Varas-Godoy , Diego Herrera-Sepulveda , Mauricio A. Retamal

Connexins (Cxs) are a family of proteins that form two different types of ion channels: hemichannels and gap junction channels. These channels participate in cellular communication, enabling them to share information and act as a synchronized syncytium. This cellular communication has been considered a strong tumor suppressor, but it is now recognized that some type of Cxs can be pro-tumorigenic. For example, Cx46 expression is increased in human breast cancer samples and correlates with cancer stem cell (CSC) characteristics in human glioma. Thus, we explored whether Cx46 and glioma cells, can set up CSC and epithelial-to-mesenchymal transition (EMT) properties in a breast cancer cell line. To this end, we transfected MCF-7 cells with Cx46 attached to a green fluorescent protein (Cx46GFP), and we determined how its expression orchestrates both the gene-expression and functional changes associated with CSC and EMT. We observed that Cx46GFP increased Sox2, Nanog, and OCT4 mRNA levels associated with a high capacity to form monoclonal colonies and tumorspheres. Similarly, Cx46GFP increased the mRNA levels of n-cadherin, Vimentin, Snail and Zeb1 to a higher migratory and invasive capacity. Furthermore, Cx46GFP transfected in MCF-7 cells induced the release of higher amounts of VEGF, which promoted angiogenesis in HUVEC cells. We demonstrated for the first time that Cx46 modulates CSC and EMT properties in breast cancer cells and thus could be relevant in the design of future cancer therapies.

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Acute activation of hemichannels by ethanol leads to Ca2+-dependent gliotransmitter release in astrocytes

2024 , Gonzalo I. Gómez , Claudia García-Rodríguez , Jesús E. Marillán , Sergio A. Vergara , Tanhia F. Alvear , Arantza Farias-Pasten , Juan C. Sáez , RETAMAL LUCERO, MAURICIO ANTONIO , Maximiliano Rovegno , Fernando C. Ortiz , Juan A. Orellana

Multiple studies have demonstrated that acute ethanol consumption alters brain function and cognition. Nevertheless, the mechanisms underlying this phenomenon remain poorly understood. Astrocyte-mediated gliotransmission is crucial for hippocampal plasticity, and recently, the opening of hemichannels has been found to play a relevant role in this process. Hemichannels are plasma membrane channels composed of six connexins or seven pannexins, respectively, that oligomerize around a central pore. They serve as ionic and molecular exchange conduits between the cytoplasm and extracellular milieu, allowing the release of various paracrine substances, such as ATP, D-serine, and glutamate, and the entry of ions and other substances, such as Ca2+ and glucose. The persistent and exacerbated opening of hemichannels has been associated with the pathogenesis and progression of several brain diseases for at least three mechanisms. The uncontrolled activity of these channels could favor the collapse of ionic gradients and osmotic balance, the release of toxic levels of ATP or glutamate, cell swelling and plasma membrane breakdown and intracellular Ca2+ overload. Here, we evaluated whether acute ethanol exposure affects the activity of astrocyte hemichannels and the possible repercussions of this phenomenon on cytoplasmatic Ca2+ signaling and gliotransmitter release. Acute ethanol exposure triggered the rapid activation of connexin43 and pannexin1 hemichannels in astrocytes, as measured by time-lapse recordings of ethidium uptake. This heightened activity derived from a rapid rise in [Ca2+]i linked to extracellular Ca2+ influx and IP3-evoked Ca2+ release from intracellular Ca2+ stores. Relevantly, the acute ethanol-induced activation of hemichannels contributed to a persistent secondary increase in [Ca2+]i. The [Ca2+]i-dependent activation of hemichannels elicited by ethanol caused the increased release of ATP and glutamate in astroglial cultures and brain slices. Our findings offer fresh perspectives on the potential mechanisms behind acute alcohol-induced brain abnormalities and propose targeting connexin43 and pannexin1 hemichannels in astrocytes as a promising avenue to prevent deleterious consequences of alcohol consumption.

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Regulation of Connexins Expression Levels by MicroRNAs, an Update

2016 , CALDERON GIADROSIC, JUAN FRANCISCO , Mauricio A. Retamal

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