title: Acoustic overstimulation modifies Mcl-1 expression in cochlear sensory epithelial cells.
abstract: Acoustic overstimulation causes apoptotic cell death in the cochlea. This death process is mediated, in part, by the mitochondrial signaling pathway involving Bcl-2 family proteins. Myeloid cell leukemia sequence 1 (Mcl-l) is an antiapoptotic member of the Bcl-2 family. Its involvement in noise-induced hair cell death has not been characterized. Here we report the endogenous expression and the noise-induced expression of Mcl-1 in Sprague Dawley rat cochleae. In the sensory epithelia of normal cochleae, there is strong constitutive expression of Mcl-1 mRNA, with an expression level higher than that of many other Bcl-2 family genes. The Mcl-1 protein is preferentially expressed in outer hair cells. After exposure to a high level of continuous noise at 115-dB sound pressure level for 1 hr, Mcl-1 expression displays a time-dependent alteration, with up-regulation of Mcl-1 mRNA at 4 hr postexposure and protein up-regulation at 1 day postexposure. Western blot analysis reveals the up-regulated Mcl-1 as the full-length form of Mcl-1. Immunolabeling of the Mcl-1 protein reveals the early increase in Mcl-1 immunoreactivity in the nuclear region of the hair cells displaying apoptotic phenotypes and a subsequent increase in survival hair cells. These results suggest that Mcl-1 is involved in the regulation of hair cell pathogenesis resulting from acoustic stress, possibly by influencing the nuclear events of apoptosis.
authors.affiliation: Center for Hearing and Deafness, State University of New York at Buffalo, Buffalo, New York 14214, USA. bhu@buffalo.edu
authors.forename: Bo Hua
authors.initials: BH
authors.lastname: Hu
authors.forename: Qunfeng
authors.initials: Q
authors.lastname: Cai
mesh_terms: D000161:Acoustic Stimulation / Q000379:methods*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001522:Behavior, Animal; D003051:Cochlea / Q000166:cytology* / Q000378:metabolism*; D004847:Epithelial Cells / Q000378:metabolism*; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D009622:Noise / Q000009:adverse effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D011571:Psychoacoustics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: C579093:Mcl1 protein, rat; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger