The influences of sphingolipid metabolites on gentamicin-induced hair cell loss of the rat cochlea.
Summary of "The influences of sphingolipid metabolites on gentamicin-induced hair cell loss of the rat cochlea."
Sphingolipid metabolites inducing ceramide, sphingosine, and sphingosine-1-phosphate (S1P) play important roles in the regulation of cell proliferation, survival, and death. Aminoglycoside antibiotics including gentamicin induce inner ear hair cell loss and sensorineural hearing loss. Apoptotic cell death is considered to play a key role in this injury. The present study was designed to investigate the possible involvement of ceramide and S1P in hair cell death due to gentamicin. In addition, the effects of other metabolites of ceramide, gangliosides GM1 (GM1) and GM3 (GM3), on gentamicin ototoxicity were also investigated. Basal turn organ of Corti explants from p3 to p5 rats were maintained in tissue culture and exposed to 20 or 35muM gentamicin for 48hours. The effects of ceramide, S1P, GM1, and GM3 on gentamicin-induced hair cell loss were examined. Gentamicin-induced hair cell loss was increased by ceramide but was decreased by S1P. GM1 and GM3 exhibited protective effects against gentamicin-induced hair cell death at the limited concentrations. These results indicate that ceramide enhances gentamicin ototoxicity by promoting apoptotic hair cell death, and that S1P, GM1, and GM3 act as cochlear protectants. In conclusion, sphingolipid metabolites influence the apoptotic reaction of hair cells to gentamicin ototoxicity.
Affiliation
Department of Otolaryngology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Japan.
Journal Details
This article was published in the following journal.
Name: Neuroscience letters
ISSN: 1872-7972
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20709153
- DOI: http://dx.doi.org/10.1016/j.neulet.2010.08.014
Medical and Biotech [MESH] Definitions
Sisomicin
Antibiotic produced by Micromonospora inyoensis. It is closely related to gentamicin C1A, one of the components of the gentamicin complex (GENTAMICINS).
Hair Cells, Auditory
Sensory cells in the organ of Corti, characterized by their apical stereocilia (hair-like projections). The inner and outer hair cells, as defined by their proximity to the core of spongy bone (the modiolus), change morphologically along the cochlea. Towards the cochlear apex, the length of hair cell bodies and their apical stereocilia increase, allowing differential responses to various frequencies of sound.
Electroporation
A technique in which electric pulses of intensity in kilovolts per centimeter and of microsecond-to-millisecond duration cause a temporary loss of the semipermeability of CELL MEMBRANES, thus leading to ion leakage, escape of metabolites, and increased uptake by cells of drugs, molecular probes, and DNA.
Progeria
An abnormal congenital condition, associated with defects in the LAMIN TYPE A gene, which is characterized by premature aging in children, where all the changes of cell senescence occur. It is manifested by premature greying; hair loss; hearing loss (DEAFNESS); cataracts (CATARACT); ARTHRITIS; OSTEOPOROSIS; DIABETES MELLITUS; atrophy of subcutaneous fat; skeletal hypoplasia; elevated urinary HYALURONIC ACID; and accelerated ATHEROSCLEROSIS. Many affected individuals develop malignant tumors, especially SARCOMA.
Hearing Loss, Noise-induced
Hearing loss due to exposure to explosive loud noise or chronic exposure to sound level greater than 85 dB. The hearing loss is often in the frequency range 4000-6000 hertz.
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