title: Modulation of Mcl-1 expression reduces age-related cochlear degeneration.
abstract: Mcl-1 is an anti-apoptotic member of the Bcl-2 family that modulates apoptosis-related signaling pathways and promotes cell survival. We have previously demonstrated a reduction of Mcl-1 expression in aging cochleae. To investigate whether restoring Mcl-1 expression would reduce aging-related cochlear degeneration, we developed a rat model of Mcl-1 overexpression. A plasmid encoding human Mcl-1/enhanced green fluorescent protein was applied to the round window of the cochlea. This in vivo treatment transfected both the sensory and supporting cells of the cochlear sensory epithelium and enhanced Mcl-1 expression at both the mRNA and the protein level. The upregulation of Mcl-1 expression reduced the progression of age-related cochlear dysfunction and sensory cell death. Furthermore, the transfection of Mcl-1 exerted its protective effect by suppressing cochlear apoptosis at the mitochondrial level. This study demonstrates that the genetic modulation of Mcl-1 expression reduces the progression of age-related cochlear degeneration.
authors.affiliation: Institute of Otolaryngology, Chinese PLA General Hospital, Beijing, People's Republic of China.
authors.forename: Wei Ping
authors.initials: WP
authors.lastname: Yang
authors.forename: Yang
authors.initials: Y
authors.lastname: Xu
authors.forename: Wei Wei
authors.initials: WW
authors.lastname: Guo
authors.forename: Hui Zhan
authors.initials: HZ
authors.lastname: Liu
authors.forename: Bo Hua
authors.initials: BH
authors.lastname: Hu
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics / Q000378:metabolism*; D000367:Age Factors; D000375:Aging / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000235:genetics; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D003051:Cochlea / Q000378:metabolism* / Q000473:pathology*; D000073840:Copper-Transporting ATPases; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005260:Female; D049452:Green Fluorescent Proteins / Q000235:genetics; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000378:metabolism / Q000473:pathology*; D014162:Transfection; D015854:Up-Regulation / Q000235:genetics
chemical_list: D027682:Cation Transport Proteins; D049452:Green Fluorescent Proteins; D000251:Adenosine Triphosphatases; C081184:ATP7A protein, human; D000073840:Copper-Transporting ATPases
keywords: Aging; Cochlea; Gene delivery; Hair cells; Intervention; Mcl-1; Rat