TY - JOUR
T1 - SiRNA-mediated knock-down of NOX3
T2 - Therapy for hearing loss?
AU - Rybak, Leonard P.
AU - Mukherjea, Debashree
AU - Jajoo, Sarvesh
AU - Kaur, Tejbeer
AU - Ramkumar, Vickram
N1 - Funding Information:
The authors are supported by grants from the National Institutes of Health (NIH), the National Institute for Deafness and other Communicative Disorders (NIDCD) grant R01-DC 02396 (L.P.R.) and F32 DC 009950 (D.M.).
PY - 2012/7
Y1 - 2012/7
N2 - Cisplatin is a widely used chemotherapeutic agent that causes significant hearing loss. Previous studies have shown that cisplatin exposure is associated with increase in reactive oxygen species (ROS) in the cochlea. The inner ear expresses a unique isoform of NADPH oxidase, NOX3. This enzyme may be the primary source of ROS generation in the cochlea. The knockdown of NOX3 by pretreatment with siRNA prevented cisplatin ototoxicity, as demonstrated by preservation of hearing thresholds and inner ear sensory cells. Trans-tympanic NOX3 siRNA reduced the expression of NOX3 and biomarkers of cochlear damage, including transient receptor vanilloid 1 (TRPV1) channel and kidney injury molecule-1 (KIM-1) in cochlear tissues. In addition, siRNA against NOX3 reduced apoptosis as demonstrated by TUNEL staining, and prevented the increased expression of Bax and abrogated the decrease in Bcl2 expression following cisplatin administration. Trans-tympanic administration of siRNA directed against NOX3 may provide a useful method of attenuating cisplatin ototoxicity. In this paper, we review recent publications dealing with the role of NOX3 in ototoxicity and the effects of siRNA against cisplatin-induced hearing loss.
AB - Cisplatin is a widely used chemotherapeutic agent that causes significant hearing loss. Previous studies have shown that cisplatin exposure is associated with increase in reactive oxygen species (ROS) in the cochlea. The inner ear expresses a unique isoform of NADPH oxidase, NOX3. This enzyme may be the primary source of ROS generation in the cochlea. The knockdown of NOX3 by pretreatment with siRNA prevented cisplatin ototoxicity, as demonstrated by preservation of hearing thresholds and inner ear sensory cells. Trans-tympanic NOX3 siRNA reduced the expression of NOX3 and biomarkers of cochlear damage, including transient receptor vanilloid 1 (TRPV1) channel and kidney injury molecule-1 (KIM-1) in cochlear tissues. In addition, siRNA against NOX3 reduced apoptosis as demonstrated by TUNEL staining, and prevented the increased expression of Bax and abrogated the decrease in Bcl2 expression following cisplatin administration. Trans-tympanic administration of siRNA directed against NOX3 may provide a useful method of attenuating cisplatin ototoxicity. In this paper, we review recent publications dealing with the role of NOX3 in ototoxicity and the effects of siRNA against cisplatin-induced hearing loss.
UR - http://www.scopus.com/inward/record.url?scp=84864375987&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84864375987&partnerID=8YFLogxK
U2 - 10.1007/s00018-012-1016-3
DO - 10.1007/s00018-012-1016-3
M3 - Review article
C2 - 22562580
AN - SCOPUS:84864375987
VL - 69
SP - 2429
EP - 2434
JO - Cellular and Molecular Life Sciences
JF - Cellular and Molecular Life Sciences
SN - 1420-682X
IS - 14
ER -