Document Detail

TRPV4 enhances the cellular uptake of aminoglycoside antibiotics.
MedLine Citation:
PMID:  18682499     Owner:  NLM     Status:  MEDLINE    
The cochlea and kidney are susceptible to aminoglycoside-induced toxicity. The non-selective cation channel TRPV4 is expressed in kidney distal tubule cells, and hair cells and the stria vascularis in the inner ear. To determine whether TRPV4 is involved in aminoglycoside trafficking, we generated a murine proximal-tubule cell line (KPT2) and a distal-tubule cell line (KDT3). TRPV4 expression was confirmed in KDT3 cells but not in KPT2 cells. Removal of extracellular Ca(2+) significantly enhanced gentamicin-Texas-Red (GTTR) uptake by KDT3, indicative of permeation through non-selective cation channels. To determine whether TRPV4 is permeable to GTTR, stable cell lines were generated that express TRPV4 in KPT2 (KPT2-TRPV4). KPT2-TRPV4 cells took up more GTTR than control cell lines (KPT2-pBabe) in the absence of extracellular Ca(2+). TRPV4-dependent GTTR uptake was abolished by a point mutation within the crucial pore region of the channel, suggesting that GTTR permeates the TRPV4 channel. In an endolymph-like extracellular environment, clearance of GTTR was attenuated from KPT2-TRPV4 cells in a TRPV4-dependent fashion. We propose that TRPV4 has a role in aminoglycoside uptake and retention in the cochlea.
Takatoshi Karasawa; Qi Wang; Yi Fu; David M Cohen; Peter S Steyger
Related Documents :
18719609 - Markers to evaluate the quality and self-renewing potential of engineered human skin su...
9879399 - Cycloheximide blocks the toxic effect of streptomycin in guinea pig vestibular hair cells.
11559899 - The inner ear macular sensory epithelia of the daubenton's bat.
3977089 - The relation of nucleolus diameter to cell body diameter in mammalian dorsal root gangl...
6783729 - Ultrastructural aspect of size dependent regulation of surface pattern of complex cilia...
1313059 - Creatine kinase in epithelium of the inner ear.
15725629 - Alleviation of benzo[a]pyrene-diolepoxide-dna damage in human lung carcinoma by glutath...
22572619 - Pterostilbene induces mitochondrially derived apoptosis in breast cancer cells in vitro.
6322839 - Photoaffinity labeling of parathyroid hormone receptors: comparison of receptors across...
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2008-08-05
Journal Detail:
Title:  Journal of cell science     Volume:  121     ISSN:  0021-9533     ISO Abbreviation:  J. Cell. Sci.     Publication Date:  2008 Sep 
Date Detail:
Created Date:  2008-08-21     Completed Date:  2008-10-30     Revised Date:  2014-09-13    
Medline Journal Info:
Nlm Unique ID:  0052457     Medline TA:  J Cell Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  2871-9     Citation Subset:  IM    
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Aminoglycosides / metabolism*
Anti-Bacterial Agents / metabolism*
Calcium / pharmacology
Cell Line
Ear, Inner / cytology,  metabolism
Endolymph / drug effects,  metabolism
Extracellular Space / drug effects,  metabolism
Gentamicins / metabolism
Kidney / cytology,  metabolism
Methionine / metabolism
TRPV Cation Channels / metabolism*
Xanthenes / metabolism
Grant Support
DC04555/DC/NIDCD NIH HHS; F32 DC008465/DC/NIDCD NIH HHS; F32 DC008465/DC/NIDCD NIH HHS; F32 DC008465-01A1/DC/NIDCD NIH HHS; F32 DC008465-02/DC/NIDCD NIH HHS; P30 DC005983/DC/NIDCD NIH HHS; P30 DC005983-03/DC/NIDCD NIH HHS; P30 DC005983-04/DC/NIDCD NIH HHS; P30 DC005983-05/DC/NIDCD NIH HHS; P30 DC05983/DC/NIDCD NIH HHS; R01 DC004555/DC/NIDCD NIH HHS; R01 DC004555-04/DC/NIDCD NIH HHS; R01 DC004555-05/DC/NIDCD NIH HHS; T32 DC005945/DC/NIDCD NIH HHS
Reg. No./Substance:
0/Aminoglycosides; 0/Anti-Bacterial Agents; 0/Gentamicins; 0/TRPV Cation Channels; 0/Trpv4 protein, rat; 0/Xanthenes; 82354-19-6/Texas red; AE28F7PNPL/Methionine; SY7Q814VUP/Calcium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Previous Document:  Cdk5 kinase regulates the association between adaptor protein Bem1 and GEF Cdc24 in the fungus Ustil...
Next Document:  High-circulating leptin levels are associated with greater risk of hypertension in men independently...