Dataset Information

In vitro gentamicin exposure alters caveolae protein profile in cochlear spiral ligament pericytes.

ABSTRACT: Background:The aminoglycoside antibiotic gentamicin is an ototoxic drug and has been used experimentally to investigate cochlear damage induced by noise.We have investigated the changes in the protein profile associated with caveolae in gentamicin treated and untreated spiral ligament (SL) pericytes, specialized cells in the blood labyrinth barrier of the inner ear microvasculature. Pericytes from various microvascular beds express caveolae, protein and cholesterol rich microdomains, which can undergo endocytosis and transcytosis to transport small molecules in and out the cells. A different protein profile in transport-specialized caveolae may induce pathological changes affecting the integrity of the blood labyrinth barrier and ultimately contributing to hearing loss. Method:Caveolae isolation from treated and untreated cells is achieved through ultracentrifugation of the lysates in discontinuous gradients. Mass spectrometry (LC-MS/MS) analysis identifies the proteins in the two groups. Proteins segregating with caveolae isolated from untreated SL pericytes are then compared to caveolae isolated from SL pericytes treated with the gentamicin for 24 h. Data are analyzed using bioinformatic tools. Results:The caveolae proteome in gentamicin treated cells shows that 40% of total proteins are uniquely associated with caveolae during the treatment, and 15% of the proteins normally associated with caveolae in untreated cell are suppressed. Bioinformatic analysis of the data shows a decreased expression of proteins involved in genetic information processing, and an increase in proteins involved in metabolism, vesicular transport and signal transduction in gentamicin treated cells. Several Rab GTPases proteins, ubiquitous transporters, uniquely segregate with caveolae and are significantly enriched in gentamicin treated cells. Conclusion:We report that gentamicin exposure modifies protein profile of caveolae from SL pericytes. We identified a pool of proteins which are uniquely segregating with caveolae during the treatment, mainly participating in metabolic and biosynthetic pathways, in transport pathways and in genetic information processing. Finally, we show for the first time proteins associated with caveolae SL pericytes linked to nonsyndromic hearing loss.

SUBMITTER: Ghelfi E

PROVIDER: S-EPMC5938607 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

In vitro gentamicin exposure alters caveolae protein profile in cochlear spiral ligament pericytes.

Ghelfi Elisa E Grondin Yohann Y Millet Emil J EJ Bartos Adam A Bortoni Magda M Oliveira Gomes Dos Santos Clara C Trevino-Villarreal Humberto J HJ Sepulveda Rosalinda R Rogers Rick R

Proteome science 20180316

<h4>Background</h4>The aminoglycoside antibiotic gentamicin is an ototoxic drug and has been used experimentally to investigate cochlear damage induced by noise.We have investigated the changes in the protein profile associated with caveolae in gentamicin treated and untreated spiral ligament (SL) pericytes, specialized cells in the blood labyrinth barrier of the inner ear microvasculature. Pericytes from various microvascular beds express caveolae, protein and cholesterol rich microdomains, whi ...[more]

PMID: 29760588

Similar Datasets

Project description:The goals of this study were to derive a frequency-position function for the human cochlear spiral ganglion (SG) to correlate represented frequency along the organ of Corti (OC) to location along the SG, to determine the range of individual variability, and to calculate an "average" frequency map (based on the trajectories of the dendrites of the SG cells). For both OC and SG frequency maps, a potentially important limitation is that accurate estimates of cochlear place frequency based upon the Greenwood function require knowledge of the total OC or SG length, which cannot be determined in most temporal bone and imaging studies. Therefore, an additional goal of this study was to evaluate a simple metric, basal coil diameter that might be utilized to estimate OC and SG length. Cadaver cochleae (n = 9) were fixed <24 h postmortem, stained with osmium tetroxide, microdissected, decalcified briefly, embedded in epoxy resin, and examined in surface preparations. In digital images, the OC and SG were measured, and the radial nerve fiber trajectories were traced to define a series of frequency-matched coordinates along the two structures. Images of the cochlear turns were reconstructed and measurements of basal turn diameter were made and correlated with OC and SG measurements. The data obtained provide a mathematical function for relating represented frequency along the OC to that of the SG. Results showed that whereas the distance along the OC that corresponds to a critical bandwidth is assumed to be constant throughout the cochlea, estimated critical band distance in the SG varies significantly along the spiral. Additional findings suggest that measurements of basal coil diameter in preoperative images may allow prediction of OC/SG length and estimation of the insertion depth required to reach specific angles of rotation and frequencies. Results also indicate that OC and SG percentage length expressed as a function of rotation angle from the round window is fairly constant across subjects. The implications of these findings for the design and surgical insertion of cochlear implants are discussed.

Dataset Information

In vitro gentamicin exposure alters caveolae protein profile in cochlear spiral ligament pericytes.

Publications

In vitro gentamicin exposure alters caveolae protein profile in cochlear spiral ligament pericytes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets