Increase in glutamate-aspartate transporter (GLAST) mRNA during kanamycin-induced cochlear insult in rats.
Kanamycin (KM)-induced changes in expression of the gene for glutamate-aspartate transporter (GLAST) in the rat cochlea were analyzed by Northern blotting. With the administration of KM (600 mg/kg/day) once daily for 20 days, the expression of GLAST mRNA gradually increased and reached a peak on day 20. Although the expression of GLAST mRNA remained at a high level until 12 days after the completion of the KM treatment, it then fell to the normal level within 2 months. Such KM treatment resulted in loss of both inner and outer hair cells and a concomitant profound permanent threshold shift. The present findings suggest that during KM administration, high concentrations of extracellular glutamate released by collapsing hair cells induced GLAST mRNA expression. Increased GLAST mRNA might play an important role in the prevention of the secondary death of spiral ganglion neurons from glutamate neurotoxicity.
Department of Otorhinolaryngology, Miyazaki Medical College, Japan. angler@post.miyazaki-med.ac.jp
K
K
Matsuda
Y
Y
Ueda
T
T
Doi
T
T
Tono
A
A
Haruta
K
K
Toyama
S
S
Komune
D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D027322:Amino Acid Transport System X-AG; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D001224:Aspartic Acid / Q000378:metabolism; D001483:Base Sequence; D003051:Cochlea / Q000187:drug effects* / Q000293:injuries / Q000378:metabolism*; D017931:DNA Primers / Q000235:genetics; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D018698:Glutamic Acid / Q000378:metabolism; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D007612:Kanamycin / Q000633:toxicity*; D008297:Male; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D018528:ATP-Binding Cassette Transporters; D027322:Amino Acid Transport System X-AG; D000900:Anti-Bacterial Agents; D017931:DNA Primers; D012333:RNA, Messenger; D001224:Aspartic Acid; D018698:Glutamic Acid; D007612:Kanamycin