PMID- 25076226
OWN - NLM
STAT- MEDLINE
DCOM- 20150722
LR  - 20181231
IS  - 1537-4505 (Electronic)
IS  - 1531-7129 (Linking)
VI  - 36
IP  - 3
DP  - 2015 Mar
TI  - Evaluation of apoptotic markers in HEI-OC1 cells treated with gentamicin with and 
      without the mitochondria-targeted antioxidant mitoquinone.
PG  - 526-30
LID - 10.1097/MAO.0000000000000517 [doi]
AB  - HYPOTHESIS: Mitoquinone (MitoQ) attenuates aminoglycoside (AG)-induced 
      upregulation of the proapoptotic molecules Bak and harakiri (Hrk) and decreases 
      the percentage of apoptotic House Ear Institute Organ of Corti 1 (HEI-OC1) cells. 
      BACKGROUND: The primary mechanism of AG ototoxicity is the formation of reactive 
      oxygen species, which leads to hair cell death via apoptotic and nonapoptotic 
      pathways. Antioxidants have been shown to protect against AG ototoxicity. 
      Mitoquinone is a mitochondria-targeted derivative of the antioxidant ubiquinone. 
      Thus, MitoQ may be more effective in preventing AG ototoxicity compared with 
      untargeted antioxidants. METHODS: Ribonucleic acid from untreated HEI-OC1 cells 
      and cells exposed to gentamicin with and without preincubation with MitoQ, 
      idebenone (IDB, an untargeted ubiquinone), or decylTPP (positive control) were 
      used to assess gene expression of Bak and Hrk using real-time polymerase chain 
      reaction. Protein expression of Bak and Hrk was determined by Western blotting. 
      Annexin V assay using flow cytometry was performed to assess the percentage of 
      apoptotic HEI-OC1 cells treated with gentamicin with and without preincubation 
      with MitoQ, decylTPP, or IDB. RESULTS: Preincubation of HEI-OC1 cells with MitoQ 
      significantly decreased the gentamicin-induced upregulation of Bak gene (p = 
      0.03) but not preincubation with IDB (p = 0.87). Harakiri levels were very low 
      that relative quantification could not be carried out. Protein levels of Bak and 
      Hrk were not different between treatments. Annexin V assay showed that gentamicin 
      increased the percentage of apoptotic cells (p < 0.05) compared with control. 
      However, the percentages of apoptotic cells in gentamicin-treated and cells 
      pretreated with the antioxidants MitoQ or IDB were not different. CONCLUSION: 
      Mitoquinone attenuated the gentamicin-induced upregulation of the Bak gene but 
      not its product, the proapoptotic molecule Bak, and MitoQ did not significantly 
      decrease the gentamicin-induced cell apoptosis in vitro. Further in vivo studies 
      are needed to assess the clinical significance of these findings.
FAU - Jadidian, Armon
AU  - Jadidian A
AD  - Department of Otolaryngology-Head and Neck Surgery, University of Florida College 
      of Medicine, Gainesville, Florida, U.S.A.
FAU - Antonelli, Patrick J
AU  - Antonelli PJ
FAU - Ojano-Dirain, Carolyn P
AU  - Ojano-Dirain CP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Otol Neurotol
JT  - Otology & neurotology : official publication of the American Otological Society, 
      American Neurotology Society [and] European Academy of Otology and Neurotology
JID - 100961504
RN  - 0 (Antioxidants)
RN  - 0 (Apoptosis Regulatory Proteins)
RN  - 0 (Gentamicins)
RN  - 0 (HRK protein, human)
RN  - 0 (Organophosphorus Compounds)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (bcl-2-Associated X Protein)
RN  - 1339-63-5 (Ubiquinone)
RN  - 47BYS17IY0 (mitoquinone)
RN  - HB6PN45W4J (idebenone)
SB  - IM
MH  - Antioxidants/*pharmacology
MH  - Apoptosis/*drug effects/physiology
MH  - Apoptosis Regulatory Proteins/metabolism
MH  - Cell Line
MH  - Gentamicins/*pharmacology
MH  - Hair Cells, Auditory/*drug effects/metabolism
MH  - Humans
MH  - Mitochondria/*drug effects/metabolism
MH  - Organophosphorus Compounds/*pharmacology
MH  - Reactive Oxygen Species/metabolism
MH  - Real-Time Polymerase Chain Reaction
MH  - Ubiquinone/*analogs & derivatives/pharmacology
MH  - bcl-2-Associated X Protein/metabolism
EDAT- 2014/07/31 06:00
MHDA- 2015/07/23 06:00
CRDT- 2014/07/31 06:00
PHST- 2014/07/31 06:00 [entrez]
PHST- 2014/07/31 06:00 [pubmed]
PHST- 2015/07/23 06:00 [medline]
AID - 10.1097/MAO.0000000000000517 [doi]
PST - ppublish
SO  - Otol Neurotol. 2015 Mar;36(3):526-30. doi: 10.1097/MAO.0000000000000517.