Acoustic overstimulation modifies Mcl-1 expression in cochlear sensory epithelial cells.
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.
Hu
Bo Hua
BH
Center for Hearing and Deafness, State University of New York at Buffalo, Buffalo, New York 14214, USA. bhu@buffalo.edu
Cai
Qunfeng
Q
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
C579093:Mcl1 protein, rat; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger