Death mode-dependent reduction in succinate dehydrogenase activity in hair cells of aging rat cochleae.
BACKGROUND
Our previous studies have shown that both apoptosis and necrosis are involved in hair cell (HC) pathogenesis in aging cochleae. To better understand the biological mechanisms responsible for the regulation of HC death, we examined the activity of succinate dehydrogenase (SDH), a mitochondrial bioenergetic enzyme, in the HCs of aging cochleae.


METHODS
The auditory brainstem response thresholds elicited by tone bursts at 4, 10 and 20 kHz were measured in both young (2-3 months) and aging (22-23 months) Wistar rats. SDH activity was evaluated with a colorimetric assay using nitroblue tetrazolium monosodium salt. The SDH-labeled organs of Corti were double stained with propidium iodide, a DNA intercalating fluorescent probe for illustration of HC nuclei. All the specimens were examined with fluorescence microscopy and confocal microscopy.


RESULTS
Aging rats exhibited a significant elevation of ABR thresholds with threshold shifts being 34 dB at 20 kHz, 28 dB at 10 kHz, and 25 dB at 4 kHz. Consistent with the reduction in the cochlear function, aging cochleae exhibited the reduction of SDH staining intensity in the apical and the basal ends of the cochleae, where a large number of apoptotic, necrotic, and missing HCs were evident. The reduction in SDH staining appeared in a cell-death-mode dependent fashion. Specifically, SDH labeling remained in apoptotic HCs. In contrast, SDH staining was markedly reduced or absent in necrotic HCs.


CONCLUSIONS
In the aging cochlea, SDH activity is preserved in HCs undergoing apoptosis, but is substantially reduced in necrosis. These results suggest that mitochondrial energetic function is involved in the regulation of cell death pathways in the pathogenesis of aging cochleae.
Yang
Wei-Ping
WP
Institute of Otolaryngology, People's Liberation Army General Hospital, Beijing 100853, China. yangwp2002@yahoo.com
Hu
Bo-Hua
BH
Sun
Jian-He
JH
Zhai
Suo-Qiang
SQ
Henderson
Donald
D
D000375:Aging / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D003051:Cochlea / Q000166:cytology* / Q000201:enzymology*; D005260:Female; D006198:Hair Cells, Auditory / Q000201:enzymology*; D008297:Male; D009336:Necrosis / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000378:metabolism*
D013385:Succinate Dehydrogenase