RETAMAL LUCERO, MAURICIO ANTONIO
Thumbnail Image
Preferred name
RETAMAL LUCERO, MAURICIO ANTONIO
Main Affiliation
Email
mretamal@udd.cl
ORCID
Scopus Author ID
8502472600

Research Output

2023 2023 2022 2022 2021 2021 2020 2020 2019 2019 2018 2018 2017 2017 2016 2016 2015 2015 2014 2014 0.0 0.0 0.5 0.5 1.0 1.0 1.5 1.5 2.0 2.0 2.5 2.5 3.0 3.0

Filters

11
11
Reset filters

Settings
Now showing 1 - 10 of 11
No Thumbnail Available
Publication

Extracellular Cysteine in Connexins: Role as Redox Sensors

2016 , RETAMAL LUCERO, MAURICIO ANTONIO , Isaac E. García , Bernardo I. Pinto , Amaury Pupo , David Báez , Jimmy Stehberg , Rodrigo Del Rio , Carlos González

View
No Thumbnail Available
Publication

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

View
No Thumbnail Available
Publication

Extracellular Cysteines Are Critical to Form Functional Cx46 Hemichannels

2022 , Ainoa Fernández-Olivares , Eduardo Durán-Jara , Daniel A. Verdugo , Mariana C. Fiori , Guillermo A. Altenberg , Jimmy Stehberg , Iván Alfaro , CALDERON GIADROSIC, JUAN FRANCISCO , Mauricio A. Retamal

Connexin (Cxs) hemichannels participate in several physiological and pathological processes, but the molecular mechanisms that control their gating remain elusive. We aimed at determining the role of extracellular cysteines (Cys) in the gating and function of Cx46 hemichannels. We studied Cx46 and mutated all of its extracellular Cys to alanine (Ala) (one at a time) and studied the effects of the Cys mutations on Cx46 expression, localization, and hemichannel activity. Wild-type Cx46 and Cys mutants were expressed at comparable levels, with similar cellular localization. However, functional experiments showed that hemichannels formed by the Cys mutants did not open either in response to membrane depolarization or removal of extracellular divalent cations. Molecular-dynamics simulations showed that Cys mutants may show a possible alteration in the electrostatic potential of the hemichannel pore and an altered disposition of important residues that could contribute to the selectivity and voltage dependency in the hemichannels. Replacement of extracellular Cys resulted in “permanently closed hemichannels”, which is congruent with the inhibition of the Cx46 hemichannel by lipid peroxides, through the oxidation of extracellular Cys. These results point to the modification of extracellular Cys as potential targets for the treatment of Cx46-hemichannel associated pathologies, such as cataracts and cancer, and may shed light into the gating mechanisms of other Cx hemichannels.

View
No Thumbnail Available
Publication

Cx46 hemichannel modulation by nitric oxide: Role of the fourth transmembrane helix cysteine and its possible involvement in cataract formation

2019 , RETAMAL LUCERO, MAURICIO ANTONIO , Orellana Villena, Viviana Paulina , Nicolás J. Arévalo , Cristóbal G. Rojas , Rodolfo J. Arjona , Constanza A. Alcaíno , Wendy González , Jonathan G. Canan , Rodrigo Moraga-Amaro , Jimmy Stehberg , Luis Reuss , Guillermo A. Altenberg

View
No Thumbnail Available
Publication

Connexin43 Hemichannels in Satellite Glial Cells, Can They Influence Sensory Neuron Activity?

2017 , RETAMAL LUCERO, MAURICIO ANTONIO , Manuel A. Riquelme , Jimmy Stehberg , Julio Alcayaga

View
No Thumbnail Available
Publication

Role of Astroglial Hemichannels and Pannexons in Memory and Neurodegenerative Diseases

2016 , Juan A. Orellana , RETAMAL LUCERO, MAURICIO ANTONIO , Rodrigo Moraga-Amaro , Jimmy Stehberg

View
No Thumbnail Available
Publication

KI04 an Aminoglycosides-Derived Molecule Acts as an Inhibitor of Human Connexin46 Hemichannels Expressed in HeLa Cells

2023 , Cheng-Wei T. Chang , Naveena Poudyal , Daniel A. Verdugo , Francisca Peña , Jimmy Stehberg , RETAMAL LUCERO, MAURICIO ANTONIO

Background: Connexins (Cxs) are proteins that help cells to communicate with the extracellular media and with the cytoplasm of neighboring cells. Despite their importance in several human physiological and pathological conditions, their pharmacology is very poor. In the last decade, some molecules derived from aminoglycosides have been developed as inhibitors of Cxs hemichannels. However, these studies have been performed in E. coli, which is a very simple model. Therefore, our main goal is to test whether these molecules have similar effects in mammalian cells. Methods: We transfected HeLa cells with the human Cx46tGFP and characterized the effect of a kanamycin-derived molecule (KI04) on Cx46 hemichannel activity by time-lapse recordings, changes in phosphorylation by Western blot, localization by epifluorescence, and possible binding sites by molecular dynamics (MD). Results: We observed that kanamycin and KI04 were the most potent inhibitors of Cx46 hemichannels among several aminoglycosides, presenting an IC50 close to 10 μM. The inhibitory effect was not associated with changes in Cx46 electrophoretic mobility or its intracellular localization. Interestingly, 5 mM DTT did not reverse KI04 inhibition, but the KI04 effect completely disappeared after washing out KI04 from the recording media. MD analysis revealed two putative binding sites of KI04 in the Cx46 hemichannel. Results: These results demonstrate that KI04 could be used as a Cx46 inhibitor and could help to develop future selective Cx46 inhibitors.

View
No Thumbnail Available
Publication

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

View
No Thumbnail Available
Publication

Peptides and peptide-derived molecules targeting the intracellular domains of Cx43: Gap junctions versus hemichannels

2013 , Jegan Iyyathurai , Catheleyne D'hondt , Nan Wang , Marijke De Bock , Bernard Himpens , RETAMAL LUCERO, MAURICIO ANTONIO , Jimmy Stehberg , Luc Leybaert , Geert Bultynck

View
No Thumbnail Available
Publication

Astroglial gliotransmitters released via Cx43 hemichannels regulate NMDAR‐dependent transmission and short‐term fear memory in the basolateral amygdala

2022 , Sergio Linsambarth , Francisco J. Carvajal , Rodrigo Moraga‐Amaro , Luis Mendez , Giovanni Tamburini , Ivanka Jimenez , Daniel Antonio Verdugo , Gonzalo I. Gómez , Nur Jury , Pablo Martínez , Brigitte Zundert , Lorena Varela‐Nallar , Mauricio A. Retamal , Claire Martin , Guillermo A. Altenberg , Mariana C. Fiori , Waldo Cerpa , Juan A. Orellana , Jimmy Stehberg

View