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c-Myb knockdown increases the neomycin-induced damage to hair-cell-like HEI-OC1 cells in vitro.
- Source :
-
Scientific reports [Sci Rep] 2017 Jan 23; Vol. 7, pp. 41094. Date of Electronic Publication: 2017 Jan 23. - Publication Year :
- 2017
-
Abstract
- c-Myb is a transcription factor that plays a key role in cell proliferation, differentiation, and apoptosis. It has been reported that c-Myb is expressed within the chicken otic placode, but whether c-Myb exists in the mammalian cochlea, and how it exerts its effects, has not been explored yet. Here, we investigated the expression of c-Myb in the postnatal mouse cochlea and HEI-OC1 cells and found that c-Myb was expressed in the hair cells (HCs) of mouse cochlea as well as in cultured HEI-OC1 cells. Next, we demonstrated that c-Myb expression was decreased in response to neomycin treatment in both cochlear HCs and HEI-OC1 cells, suggesting an otoprotective role for c-Myb. We then knocked down c-Myb expression with shRNA transfection in HEI-OC1 cells and found that c-Myb knockdown decreased cell viability, increased expression of pro-apoptotic factors, and enhanced cell apoptosis after neomycin insult. Mechanistic studies revealed that c-Myb knockdown increased cellular levels of reactive oxygen species and decreased Bcl-2 expression, both of which are likely to be responsible for the increased sensitivity of c-Myb knockdown cells to neomycin. This study provides evidence that c-Myb might serve as a new target for the prevention of aminoglycoside-induced HC loss.
- Subjects :
- Aminoglycosides pharmacology
Animals
Apoptosis drug effects
Cell Differentiation drug effects
Cell Proliferation drug effects
Cell Survival drug effects
Gene Expression Regulation drug effects
Hair Cells, Auditory drug effects
Mice
Mitochondria metabolism
Neomycin pharmacology
Proto-Oncogene Proteins c-myb antagonists & inhibitors
Reactive Oxygen Species metabolism
Hair Cells, Auditory pathology
Mitochondria drug effects
Protein Synthesis Inhibitors pharmacology
Proto-Oncogene Proteins c-myb genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 7
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 28112219
- Full Text :
- https://doi.org/10.1038/srep41094