Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2-4
pubmed:dateCreated
2007-8-6
pubmed:abstractText
Glutamate-cysteine ligase (GCL), previously known as gamma-glutamylcysteine synthetase, is the rate-limiting enzyme for GSH synthesis. The expression of GCL is mediated by activator protein-1 (AP-1) and nuclear factor-kappa B (NF-kappaB), which are known to participate in stress-induced apoptotic pathways in neuronal cells. In this study, we investigated the changes in the level of these transcription factors as well as of GCL catalytic subunit in the cochlea in response to acoustic overstimulation. Nuclear extracts were prepared from the cochlear at various time points after intense noise exposure (4kHz octave band, 125dB sound pressure level, 5h), and then determined DNA binding activity of the transcription factors. AP-1 DNA binding was markedly increased 2-12h after the noise exposure, with a peak at 2h after the exposure. NF-kappaB DNA binding was also increased immediately after the exposure. Semi-quantitative RT-PCR revealed that the catalytic subunit of GCL mRNA was elevated in the cochlea 2-24h post the exposure. Further immunohistochemical study revealed that increased level of GCL catalytic subunit observed at least in the spiral ganglion cells after the exposure. These results suggest that intense noise exposure facilitates the expression of GCL catalytic subunit in the cochlea possibly through the activation of transcription factors including AP-1 and NF-kappaB.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0197-0186
pubmed:author
pubmed:issnType
Print
pubmed:volume
51
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
209-15
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:17559975-Acoustic Stimulation, pubmed-meshheading:17559975-Animals, pubmed-meshheading:17559975-Catalytic Domain, pubmed-meshheading:17559975-Cell Death, pubmed-meshheading:17559975-Cochlea, pubmed-meshheading:17559975-DNA-Binding Proteins, pubmed-meshheading:17559975-Glutamate-Cysteine Ligase, pubmed-meshheading:17559975-Glutathione, pubmed-meshheading:17559975-Hair Cells, Auditory, pubmed-meshheading:17559975-Hearing Loss, Sensorineural, pubmed-meshheading:17559975-Male, pubmed-meshheading:17559975-Mice, pubmed-meshheading:17559975-NF-kappa B, pubmed-meshheading:17559975-Nerve Degeneration, pubmed-meshheading:17559975-Noise, pubmed-meshheading:17559975-Oxidative Stress, pubmed-meshheading:17559975-RNA, Messenger, pubmed-meshheading:17559975-Transcription Factor AP-1, pubmed-meshheading:17559975-Up-Regulation
pubmed:articleTitle
Acoustic overstimulation facilitates the expression of glutamate-cysteine ligase catalytic subunit probably through enhanced DNA binding of activator protein-1 and/or NF-kappaB in the murine cochlea.
pubmed:affiliation
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan University, 45-1 Nagaotoge-cho, Hirakata, Osaka 573-0101, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't