Cargando…
Different uptake of gentamicin through TRPV1 and TRPV4 channels determines cochlear hair cell vulnerability
Hair cells at the base of the cochlea appear to be more susceptible to damage by the aminoglycoside gentamicin than those at the apex. However, the mechanism of base-to-apex gradient ototoxicity by gentamicin remains to be elucidated. We report here that gentamicin caused rodent cochlear hair cell d...
Autores principales: | , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641395/ https://www.ncbi.nlm.nih.gov/pubmed/23470714 http://dx.doi.org/10.1038/emm.2013.25 |
_version_ | 1782268013886570496 |
---|---|
author | Lee, Jeong-Han Park, Channy Kim, Se-Jin Kim, Hyung-Jin Oh, Gi-Su Shen, AiHua So, Hong-Seob Park, Raekil |
author_facet | Lee, Jeong-Han Park, Channy Kim, Se-Jin Kim, Hyung-Jin Oh, Gi-Su Shen, AiHua So, Hong-Seob Park, Raekil |
author_sort | Lee, Jeong-Han |
collection | PubMed |
description | Hair cells at the base of the cochlea appear to be more susceptible to damage by the aminoglycoside gentamicin than those at the apex. However, the mechanism of base-to-apex gradient ototoxicity by gentamicin remains to be elucidated. We report here that gentamicin caused rodent cochlear hair cell damages in a time- and dose-dependent manner. Hair cells at the basal turn were more vulnerable to gentamicin than those at the apical turn. Gentamicin-conjugated Texas Red (GTTR) uptake was predominant in basal turn hair cells in neonatal rats. Transient receptor potential vanilloid 1 (TRPV1) and 4 (TRPV4) expression was confirmed in the cuticular plate, stereocilia and hair cell body of inner hair cells and outer hair cells. The involvement of TRPV1 and TRPV4 in gentamicin trafficking of hair cells was confirmed by exogenous calcium treatment and TRPV inhibitors, including gadolinium and ruthenium red, which resulted in markedly inhibited GTTR uptake and gentamicin-induced hair cell damage in rodent and zebrafish ototoxic model systems. These results indicate that the cytotoxic vulnerability of cochlear hair cells in the basal turn to gentamicin may depend on effective uptake of the drug, which was, in part, mediated by the TRPV1 and TRPV4 proteins. |
format | Online Article Text |
id | pubmed-3641395 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-36413952013-05-02 Different uptake of gentamicin through TRPV1 and TRPV4 channels determines cochlear hair cell vulnerability Lee, Jeong-Han Park, Channy Kim, Se-Jin Kim, Hyung-Jin Oh, Gi-Su Shen, AiHua So, Hong-Seob Park, Raekil Exp Mol Med Original Article Hair cells at the base of the cochlea appear to be more susceptible to damage by the aminoglycoside gentamicin than those at the apex. However, the mechanism of base-to-apex gradient ototoxicity by gentamicin remains to be elucidated. We report here that gentamicin caused rodent cochlear hair cell damages in a time- and dose-dependent manner. Hair cells at the basal turn were more vulnerable to gentamicin than those at the apical turn. Gentamicin-conjugated Texas Red (GTTR) uptake was predominant in basal turn hair cells in neonatal rats. Transient receptor potential vanilloid 1 (TRPV1) and 4 (TRPV4) expression was confirmed in the cuticular plate, stereocilia and hair cell body of inner hair cells and outer hair cells. The involvement of TRPV1 and TRPV4 in gentamicin trafficking of hair cells was confirmed by exogenous calcium treatment and TRPV inhibitors, including gadolinium and ruthenium red, which resulted in markedly inhibited GTTR uptake and gentamicin-induced hair cell damage in rodent and zebrafish ototoxic model systems. These results indicate that the cytotoxic vulnerability of cochlear hair cells in the basal turn to gentamicin may depend on effective uptake of the drug, which was, in part, mediated by the TRPV1 and TRPV4 proteins. Nature Publishing Group 2013-03 2013-03-08 /pmc/articles/PMC3641395/ /pubmed/23470714 http://dx.doi.org/10.1038/emm.2013.25 Text en Copyright © 2013 KSBMB. http://creativecommons.org/licenses/by-nc-nd/3.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/ |
spellingShingle | Original Article Lee, Jeong-Han Park, Channy Kim, Se-Jin Kim, Hyung-Jin Oh, Gi-Su Shen, AiHua So, Hong-Seob Park, Raekil Different uptake of gentamicin through TRPV1 and TRPV4 channels determines cochlear hair cell vulnerability |
title | Different uptake of gentamicin through TRPV1 and TRPV4 channels determines cochlear hair cell vulnerability |
title_full | Different uptake of gentamicin through TRPV1 and TRPV4 channels determines cochlear hair cell vulnerability |
title_fullStr | Different uptake of gentamicin through TRPV1 and TRPV4 channels determines cochlear hair cell vulnerability |
title_full_unstemmed | Different uptake of gentamicin through TRPV1 and TRPV4 channels determines cochlear hair cell vulnerability |
title_short | Different uptake of gentamicin through TRPV1 and TRPV4 channels determines cochlear hair cell vulnerability |
title_sort | different uptake of gentamicin through trpv1 and trpv4 channels determines cochlear hair cell vulnerability |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641395/ https://www.ncbi.nlm.nih.gov/pubmed/23470714 http://dx.doi.org/10.1038/emm.2013.25 |
work_keys_str_mv | AT leejeonghan differentuptakeofgentamicinthroughtrpv1andtrpv4channelsdeterminescochlearhaircellvulnerability AT parkchanny differentuptakeofgentamicinthroughtrpv1andtrpv4channelsdeterminescochlearhaircellvulnerability AT kimsejin differentuptakeofgentamicinthroughtrpv1andtrpv4channelsdeterminescochlearhaircellvulnerability AT kimhyungjin differentuptakeofgentamicinthroughtrpv1andtrpv4channelsdeterminescochlearhaircellvulnerability AT ohgisu differentuptakeofgentamicinthroughtrpv1andtrpv4channelsdeterminescochlearhaircellvulnerability AT shenaihua differentuptakeofgentamicinthroughtrpv1andtrpv4channelsdeterminescochlearhaircellvulnerability AT sohongseob differentuptakeofgentamicinthroughtrpv1andtrpv4channelsdeterminescochlearhaircellvulnerability AT parkraekil differentuptakeofgentamicinthroughtrpv1andtrpv4channelsdeterminescochlearhaircellvulnerability |