Show simple item record

dc.contributor.authorKim, Ye-Ri
dc.contributor.authorBaek, Jeong-In
dc.contributor.authorKim, Sung Hwan
dc.contributor.authorKim, Min-A
dc.contributor.authorLee, Byeonghyeon
dc.contributor.authorRyu, Nari
dc.contributor.authorKim, Kyung-Hee
dc.contributor.authorChoi, Deok-Gyun
dc.contributor.authorKim, Hye-Min
dc.contributor.authorMurphy, Mike
dc.contributor.authorMacpherson, Greg
dc.contributor.authorChoo, Yeon-Sik
dc.contributor.authorBok, Jinwoong
dc.contributor.authorLee, Kyu-Yup
dc.contributor.authorPark, Jeen-Woo
dc.contributor.authorKim, Un-Kyung
dc.date.accessioned2019-01-03T00:30:16Z
dc.date.available2019-01-03T00:30:16Z
dc.date.issued2019-01
dc.identifier.issn2213-2317
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287484
dc.description.abstractMitochondrial NADP+-dependent isocitrate dehydrogenase 2 (IDH2) is a major NADPH-producing enzyme which is essential for maintaining the mitochondrial redox balance in cells. We sought to determine whether IDH2 deficiency induces mitochondrial dysfunction and modulates auditory function, and investigated the protective potential of an antioxidant agent against reactive oxygen species (ROS)-induced cochlear damage in Idh2 knockout (Idh2-/-) mice. Idh2 deficiency leads to damages to hair cells and spiral ganglion neurons (SGNs) in the cochlea and ultimately to apoptotic cell death and progressive sensorineural hearing loss in Idh2-/- mice. Loss of IDH2 activity led to decreased levels of NADPH and glutathione causing abnormal ROS accumulation and oxidative damage, which might trigger apoptosis signal in hair cells and SGNs in Idh2-/- mice. We performed ex vivo experiments to determine whether administration of mitochondria-targeted antioxidants might protect or induce recovery of cells from ROS-induced apoptosis in Idh2-deficient mouse cochlea. MitoQ almost completely neutralized the H2O2-induced ototoxicity, as the survival rate of Idh2-/- hair cells were restored to normal levels. In addition, the lack of IDH2 led to the accumulation of mitochondrial ROS and the depolarization of ΔΨm, resulting in hair cell loss. In the present study, we identified that IDH2 is indispensable for the functional maintenance and survival of hair cells and SGNs. Moreover, the hair cell degeneration caused by IDH2 deficiency can be prevented by MitoQ, which suggests that Idh2-/- mice could be a valuable animal model for evaluating the therapeutic effects of various antioxidant candidates to overcome ROS-induced hearing loss.
dc.format.mediumPrint-Electronic
dc.languageeng
dc.publisherElsevier BV
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectSpiral Ganglion
dc.subjectMitochondria
dc.subjectAnimals
dc.subjectMice, Knockout
dc.subjectMice
dc.subjectHearing Loss, Sensorineural
dc.subjectDisease Models, Animal
dc.subjectReactive Oxygen Species
dc.subjectOrganophosphorus Compounds
dc.subjectUbiquinone
dc.subjectIsocitrate Dehydrogenase
dc.subjectFluorescent Antibody Technique
dc.subjectImmunohistochemistry
dc.subjectApoptosis
dc.subjectOxidation-Reduction
dc.subjectOxidative Stress
dc.subjectHomozygote
dc.subjectHair Cells, Auditory
dc.subjectBiomarkers
dc.titleTherapeutic potential of the mitochondria-targeted antioxidant MitoQ in mitochondrial-ROS induced sensorineural hearing loss caused by Idh2 deficiency.
dc.typeArticle
prism.endingPage555
prism.publicationDate2019
prism.publicationNameRedox Biol
prism.startingPage544
prism.volume20
dc.identifier.doi10.17863/CAM.34789
dcterms.dateAccepted2018-11-18
rioxxterms.versionofrecord10.1016/j.redox.2018.11.013
rioxxterms.versionVoR
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.licenseref.startdate2019-01
dc.contributor.orcidMurphy, Mike [0000-0003-1115-9618]
dc.identifier.eissn2213-2317
rioxxterms.typeJournal Article/Review
pubs.funder-project-idMedical Research Council (MC_UU_00015/3)


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International