Browsing by Author "Sanchez, Helmuth A."

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    Inflammatory conditions induce gap junctional communication between rat Kupffer cells both in vivo and in vitro
    (2007) Eugenin, Eliseo A.; Gonzalez, Hernan E.; Sanchez, Helmuth A.; Branes, Maria C.; Saez, Juan C.
    Connexin43 (Cx43), a gap junction protein subunit, has been previously detected in Kupffer cells (KCs) during liver inflammation, however, KCs phagocytose cell debris that may include Cx43 protein, which could explain the detection of Cx43 in KCs. We determined that KCs express Cx43 and form gap junctions (GJs) both in vivo and in vitro. In liver sections of animals treated with LPS, Cx43 was detected at ED2+ cells interfaces, indicating formation of GJs between KCs in vivo. In vitro, unstimulated KCs cultures did not form functional GJs, and expressed low levels of Cx43 that showed a diffuse intracellular distribution. In contrast, KCs treated with LPS plus IFN-gamma, expressed a greater amount of Cx43 at both, protein and mRNA levels, and showed Cx43 at cell-cell contacts associated with higher dye coupling. In conclusion, activation of KCs in vivo or in vitro resulted in enhanced Cx43 expression levels and formation of GJ that might play relevant roles during liver inflammation. (c) 2007 Elsevier Inc. All rights reserved.
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    MATE1 expression in the cochlea and its potential involvement in cisplatin cellular uptake and ototoxicity
    (2023) Waissbluth, Sofia; Martinez, Agustin D.; Figueroa-Cares, Cindel; Sanchez, Helmuth A.; Maass, Juan C.
    BackgroundCisplatin appears to enter the cochlear cells through the organic cation transporter 2 (OCT2). There is recent evidence that multidrug and toxin extrusion protein 1 (MATE1) is involved in cisplatin-induced nephrotoxicity. Its presence and role in the ear are unknown.Aims/ObjectivesEvaluate the presence and localization of MATE1, and determine the localization of OCT2, in the cochlea. Evaluate cisplatin uptake with regard to MATE1 and OCT2 expression.Material and MethodsMurine cochlear explants and paraffin-embedded cochleae were evaluated with immunohistochemistry for OCT2 and MATE1. Explant cultures were also treated with Texas Red cisplatin to determine their cellular uptake.ResultsMATE1 is present in the cochlea. Most intense labeling of MATE1 and OCT2 was seen in the outer hair cells (OHCs) and pillar cells, respectively. Both transporters were observed in the spiral ganglion neurons and stria vascularis. Expression levels of OCT2 and MATE1 decreased following cisplatin exposure. Texas Red cisplatin staining was strong in OHCs and pillar cells.Conclusions and SignificanceTo the best of our knowledge, this is the first study demonstrating the presence and localization of MATE1 in the cochlea. OCT2 labeling was seen in pillar cells. Consistently, OHCs and pillar cells uptake Texas Red cisplatin.
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    Supporting Cells and Their Potential Roles in Cisplatin-Induced Ototoxicity
    (2022) Waissbluth Abarca, Sofía; Maass, Juan Cristobal; Sanchez, Helmuth A.; Martinez, Agustin D.
    Cisplatin is a known ototoxic chemotherapy drug, causing irreversible hearing loss. Evidence has shown that cisplatin causes inner ear damage as a result of adduct formation, a proinflammatory environment and the generation of reactive oxygen species within the inner ear. The main cochlear targets for cisplatin are commonly known to be the outer hair cells, the stria vascularis and the spiral ganglion neurons. Further evidence has shown that certain transporters can mediate cisplatin influx into the inner ear cells including organic cation transporter 2 (OCT2) and the copper transporter Ctr1. However, the expression profiles for these transporters within inner ear cells are not consistent in the literature, and expression of OCT2 and Ctr1 has also been observed in supporting cells. Organ of Corti supporting cells are essential for hair cell activity and survival. Special interest has been devoted to gap junction expression by these cells as certain mutations have been linked to hearing loss. Interestingly, cisplatin appears to affect connexin expression in the inner ear. While investigations regarding cisplatin-induced hearing loss have been focused mainly on the known targets previously mentioned, the role of supporting cells for cisplatin-induced ototoxicity has been overlooked. In this mini review, we discuss the implications of supporting cells expressing OCT2 and Ctr1 as well as the potential role of gap junctions in cisplatin-induced cytotoxicity.