Bcl-2 genes regulate noise-induced hearing loss.
Proteins of the Bcl-2 family have been implicated in control of apoptotic pathways modulating neuronal cell death, including noise-induced hearing loss. In this study, we assessed the expressions of anti- and proapoptotic Bcl-2 genes, represented by Bcl-xL and Bak following noise exposures, which yielded temporary threshold shift (TTS) or permanent threshold shift (PTS). Auditory brainstem responses (ABRs) were assessed at 4, 8, and 16 kHz before exposure and on days 1, 3, 7, and 10 following exposure to 100 dB SPL, 4 kHz OBN, 1 hr (TTS) or 120 dB SPL, 4 kHz OBN, 5 hr (PTS). On day 10, subjects were euthanized. ABR thresholds increased following both exposures, fully recovered following the TTS exposure, and showed a 22.6 dB (4 kHz), 42.5 dB (8 kHz), and 44.9 dB (16 kHz) mean shift on day 10 following the PTS exposure. PTS was accompanied by outer hair cell loss progressing epically and basally from the 4-kHz region. Additional animals were euthanized for immunohistochemical assessment. BcL-xL was robustly expressed in outer hair cells following TTS exposure, whereas Bak was expressed following PTS exposure. These results indicate an important role of the Bcl-2 family proteins in regulating sensory cell survival or death following intense noise. Bcl-xL plays an essential role in prevention of sensory cell death following TTS levels of noise, and PTS exposure provokes the expression of Bak and, with that, cell death.
Yamashita
Daisuke
D
Kresge Hearing Research Institute, University of Michigan, Ann Arbor, Michigan 48109-0506, USA.
Minami
Shujiro B
SB
Kanzaki
Sho
S
Ogawa
Kaoru
K
Miller
Josef M
JM
D000818:Animals; D016057:Evoked Potentials, Auditory, Brain Stem / Q000502:physiology*; D019254:Genes, bcl-2; D006168:Guinea Pigs; D006198:Hair Cells, Auditory / Q000378:metabolism* / Q000473:pathology; D006317:Hearing Loss, Noise-Induced / Q000235:genetics* / Q000473:pathology; D007150:Immunohistochemistry; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis; D050998:bcl-2 Homologous Antagonist-Killer Protein / Q000096:biosynthesis
D019253:Proto-Oncogene Proteins c-bcl-2; D050998:bcl-2 Homologous Antagonist-Killer Protein