Apoptotic outer hair cell death in the cochleae of aging Fischer 344/NHsd rats.
Apoptotic cell death has been implicated in cochlear degeneration during aging. To better understand the impact and the biological process of outer hair cell (OHC) apoptosis, we investigated the contribution of apoptotic cell death to the formation of the OHC lesions, and observed the temporal patterns of the occurrence of apoptotic events associated with the mitochondrial pathway in Fischer 344/NHsd rats, with ages ranging from 20 to 27 months. The results showed that the ratio of apoptotic to necrotic OHCs was 8:1. During the process of cell degeneration, the onset of Bax expression, cytochrome c release, and nuclear DNA fragmentation preceded the onset of nuclear condensation. In contrast, the activation of caspases-3 and -9, as well as the degradation of F-actin, took place after the onset of nuclear condensation. The results of this study suggest that the initiation of nuclear degradation is a caspase-3-independent process. Moreover, the study revealed that OHCs with Bax expression or cytochrome c release could enter either the apoptotic or necrotic pathway, suggesting the presence of a regulatory mechanism that guides degenerating OHCs to die via either the apoptotic or necrotic pathway.
Hu
Bo Hua
BH
Center for Hearing and Deafness, State University of New York at Buffalo, Department of Communicative Disorders and Sciences, Buffalo, NY 14214, USA. bhu@acsu.buffalo.edu
Yang
Wei-Ping
WP
Bielefeld
Eric C
EC
Li
Manna
M
Chen
Guang-Di
GD
Henderson
Donald
D
D000199:Actins / Q000378:metabolism; D000375:Aging / Q000473:pathology* / Q000502:physiology; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D002467:Cell Nucleus / Q000473:pathology / Q000502:physiology; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D016057:Evoked Potentials, Auditory, Brain Stem; D018072:Hair Cells, Auditory, Outer / Q000473:pathology* / Q000502:physiology; D008928:Mitochondria / Q000473:pathology / Q000502:physiology; D009336:Necrosis; D051381:Rats; D011916:Rats, Inbred F344; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D000199:Actins; C494828:Bax protein, rat; D051028:bcl-2-Associated X Protein; D045304:Cytochromes c; C505410:Casp3 protein, rat; D053148:Caspase 3
Cell Mol Biol Lett. 2002;7(4):995-1018
12511968
J Biochem. 2000 Sep;128(3):463-70
10965046
Laryngoscope. 2001 Mar;111(3):528-34
11224787
Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):8461-6
9671700
J Physiol Biochem. 2003 Jun;59(2):129-41
14649878
Oncogene. 2002 Apr 18;21(17):2762-7
11965549
Dev Neurosci. 2000 Sep-Dec;22(5-6):348-58
11111150
Eur J Clin Invest. 2003 Oct;33(10):905-11
14511363
Toxicol Appl Pharmacol. 2000 Apr 1;164(1):102-11
10739750
Curr Pharm Des. 2005;11(17):2257-75
16026294
Acta Otolaryngol. 2000 Jan;120(1):19-24
10779180
Proc Natl Acad Sci U S A. 1998 Apr 28;95(9):4997-5002
9560217
Nature. 2006 Oct 12;443(7112):658-62
17035996
Clin Exp Immunol. 1997 Nov;110(2):324-8
9367420
Am J Physiol. 1998 Feb;274(2):F315-27
9486226
Hear Res. 1998 Dec;126(1-2):11-8
9872129
J Exp Med. 2000 Aug 21;192(4):571-80
10952727
Rev Laryngol Otol Rhinol (Bord). 2005;126(2):67-74
16180344
J Assoc Res Otolaryngol. 2003 Dec;4(4):466-77
14534835
Hear Res. 2002 Oct;172(1-2):1-9
12361861
Otol Neurotol. 2004 Jul;25(4):627-32
15241246
Antioxid Redox Signal. 2005 Sep-Oct;7(9-10):1092-100
16115013
EMBO J. 2002 Apr 15;21(8):1967-77
11953316
Int J Oncol. 2000 Apr;16(4):745-9
10717243
Genes Dev. 1998 Mar 15;12(6):806-19
9512515
Brain Res. 1997 Jan 30;747(1):147-50
9042539
Eur J Cell Biol. 2001 Apr;80(4):312-20
11370746
Hear Res. 2004 Oct;196(1-2):69-76
15464303
Acta Otolaryngol. 2006 Dec;126(11):1134-9
17050304
Restor Neurol Neurosci. 2005;23(1):1-9
15846027
Am J Physiol Heart Circ Physiol. 2001 Oct;281(4):H1637-47
11557554
Hear Res. 2007 Jan;223(1-2):61-70
17141990
Cancer Cell. 2005 Jul;8(1):5-6
16023593