Linked Life Data

12853430

Source:http://linkedlifedata.com/resource/pubmed/id/12853430

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
14
pubmed:dateCreated
2003-7-10
pubmed:abstractText
The sensory hair cells of the inner ear undergo apoptosis after acoustic trauma or aminoglycoside antibiotic treatment, causing permanent auditory and vestibular deficits in humans. Previous studies have demonstrated a role for caspase activation in hair cell death and ototoxic injury that can be reduced by concurrent treatment with caspase inhibitors in vitro. In this study, we examined the protective effects of caspase inhibition on hair cell death in vivo after systemic injections of aminoglycosides. In one series of experiments, chickens were implanted with osmotic pumps that administrated the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (zVAD) into inner ear fluids. One day after the surgery, the animals received a 5 d course of treatment with streptomycin, a vestibulotoxic aminoglycoside. Direct infusion of zVAD into the vestibule significantly increased hair cell survival after streptomycin treatment. A second series of experiments determined whether rescued hair cells could function as sensory receptors. Animals treated with streptomycin displayed vestibular system impairment as measured by a greatly reduced vestibulo-ocular response (VOR). In contrast, animals that received concurrent systemic administration of zVAD with streptomycin had both significantly greater hair cell survival and significantly increased VOR responses, as compared with animals treated with streptomycin alone. These findings suggest that inhibiting the activation of caspases promotes the survival of hair cells and protects against vestibular function deficits after aminoglycoside treatment.
pubmed:grant
pubmed:keyword
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1529-2401
pubmed:author
pubmed:issnType
Electronic
pubmed:day
9
pubmed:volume
23
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6111-22
pubmed:dateRevised
2011-8-1
pubmed:meshHeading
pubmed-meshheading:12853430-Amino Acid Chloromethyl Ketones, pubmed-meshheading:12853430-Aminoglycosides, pubmed-meshheading:12853430-Animals, pubmed-meshheading:12853430-Apoptosis, pubmed-meshheading:12853430-Calcium-Binding Protein, Vitamin D-Dependent, pubmed-meshheading:12853430-Caspases, pubmed-meshheading:12853430-Cell Survival, pubmed-meshheading:12853430-Chickens, pubmed-meshheading:12853430-Cysteine Proteinase Inhibitors, pubmed-meshheading:12853430-Drug Administration Routes, pubmed-meshheading:12853430-Eye Movements, pubmed-meshheading:12853430-Hair Cells, Vestibular, pubmed-meshheading:12853430-Infusion Pumps, Implantable, pubmed-meshheading:12853430-Photic Stimulation, pubmed-meshheading:12853430-Reflex, Vestibulo-Ocular, pubmed-meshheading:12853430-Rotation, pubmed-meshheading:12853430-Saccule and Utricle, pubmed-meshheading:12853430-Streptomycin
pubmed:year
2003
pubmed:articleTitle
Caspase inhibitors promote vestibular hair cell survival and function after aminoglycoside treatment in vivo.
pubmed:affiliation
Division of Biology and Biomedical Sciences, Washington University in St. Louis, St. Louis, Missouri 63110, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't