Expression analysis suggests a potential cytoprotective role of Birc5 in the inner ear.
Hearing impairment is a worldwide health problem. Employing semi-quantitative immunological detection methods, we found that the apoptosis inhibitor protein Birc5 is expressed in cell types critical for hearing perception. In the guinea pig model, moderate noise exposure causing only a temporary mean hearing impairment of 33dB significantly enhanced Birc5 expression in the spiral ligament, nerve fibers and the organ of Corti. In contrast, intratympanic gentamicin injection inducing permanent cell damage and mean hearing loss of 24dB correlated with a significant Birc5 downregulation in the ligament, nerve fibers and the organ of Corti. The cytoprotective activity of the guinea pig and human Birc5 protein was confirmed by cloning of the gene and by subsequent ectopic expression and challenging studies against the ototoxin gentamicin in epithelial and auditory cell models. As the mammalian cochlea is unable to regenerate upon damage, these data suggest that modulation of Birc5 expression may represent a novel physiological mechanism to protect the inner ear against stress-induced cell damage. Hence, the targeted modulation of Birc5 levels may lead to novel otoprotective therapeutic strategies.
Habtemichael
Negusse
N
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital of Mainz, Mainz, Germany.
Heinrich
Ulf-Rüdiger
UR
Knauer
Shirley K
SK
Schmidtmann
Irene
I
Bier
Carolin
C
Docter
Dominic
D
Brochhausen
Christoph
C
Helling
Kai
K
Brieger
Jürgen
J
Stauber
Roland H
RH
Mann
Wolf J
WJ
D000818:Animals; D002478:Cells, Cultured; D019610:Cytoprotection; D007758:Ear, Inner / Q000033:anatomy & histology / Q000502:physiology*; D005260:Female; D005839:Gentamicins / Q000633:toxicity; D006168:Guinea Pigs; D006367:HeLa Cells; D034381:Hearing Loss / Q000139:chemically induced; D006317:Hearing Loss, Noise-Induced / Q000503:physiopathology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D009622:Noise / Q000009:adverse effects; D011500:Protein Synthesis Inhibitors / Q000633:toxicity; D000077022:Survivin
C107489:BIRC5 protein, human; D005839:Gentamicins; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D011500:Protein Synthesis Inhibitors; D000077022:Survivin