Apoptosis of guinea pig cochlear hair cells following chronic aminoglycoside treatment

Nakagawa, Takayuki; Yamane, Hideo; Takayama, Masahiro; Sunami, Kishiko; Nakai, Yousuke

doi:10.1007/s004050050027

Cited by 66 publications

(35 citation statements)

References 16 publications

(29 reference statements)

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“…The reticular lamina appeared to maintain its confluence at all stages, in all preparations examined, despite the drastic cytoarchitectural changes underneath the surface. The clumps of fragmented DNA found in degenerating hair cells as early as two days after the insult resembled similar DNA clumps seen when hair cells degenerate in the avian basilar papilla, 7,8 the mammalian vestibular epithelium 9 and the organ of Corti. 9,10 The presence of the DNA clumps under a sealed reticular lamina strongly suggests that hair cells die within the epithelium.…”

Section: Discussionsupporting

confidence: 56%

Cell Division and Maintenance of Epithelial Integrity in the Deafened Auditory Epithelium

Kim¹,

Raphael²

2007

Cell Cycle

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Section: Discussionsupporting

confidence: 56%

Cell Division and Maintenance of Epithelial Integrity in the Deafened Auditory Epithelium

Kim¹,

Raphael²

2007

Cell Cycle

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“…38 A most painstaking morphological day-by-day evaluation of kanamycin ototoxicity 39 suggested the occurrence of both apoptotic and necrotic features. Following chronic aminoglycoside treatment Nakagawa et al 40 did not see apoptotic labels at the primary site of aminoglycoside toxicity, namely the basal turn of the cochlea. They speculated that 'outer hair cells of the basal turn may degenerate predominantly by necrosis'.…”

Section: Discussionmentioning

confidence: 96%

Caspase-independent pathways of hair cell death induced by kanamycin in vivo

et al. 2005

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Cochlear and vestibular sensory cells undergo apoptosis when exposed to aminoglycoside antibiotics in organ culture, but mechanisms of chronic drug-induced hair cell loss in vivo are unclear. We investigated cell death pathways in a mouse model of progressive kanamycin-induced hair cell loss. Hair cell nuclei showed both apoptotic-and necrotic-like appearances but markers for classic apoptotic pathways (cytochrome c, caspase-9, caspase-3, JNK, TUNEL) were absent. In contrast, drug treatment caused EndoG translocation, activation of l-calpain, and both the synthesis and activation of cathepsin D. Poly (ADP-ribose) polymerase 1 (PARP1) was decreased, but a caspase-derived 89 kDa PARP1 fragment was not present. The mRNA level of PARP1 remained unchanged. Thus, chronic administration of aminoglycosides causes multiple forms of cell death, without a major contribution by classic apoptosis. These results provide a better understanding of the toxic effects of aminoglycosides and are relevant to design protection from aminoglycosideinduced hearing loss.

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“…Clearance of aminoglycosides from both inner ear fluids and tissues is very slow: While the half-life of aminoglycosides in serum is about 3-5 h, they can remain in the inner ear for longer than 30 days (Tran Ba Huy et al 1986). When exposed to aminoglycosides, hair cells demonstrate both morphologic and molecular features of apoptotic cell death, including condensed, marginated chromatin, and positive terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining (Forge and Fradis 1985;Li et al 1995;Lang and Liu 1997;Nakagawa et al 1998;Forge and Li 2000;Matsui et al 2002;Mangiardi et al 2004). In addition, aminoglycoside-induced hair cell apoptosis is mediated by c-Jun N-terminal kinase (JNK), a member of the mitogenactivated protein kinase family.…”

Section: Introductionmentioning

confidence: 99%

Hsp70 inhibits aminoglycoside-induced hearing loss and cochlear hair cell death

Taleb

Brandon

Lee

et al. 2009

Cell Stress and Chaperones

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Sensory hair cells of the inner ear are sensitive to death from aging, noise trauma, and ototoxic drugs. Ototoxic drugs include the aminoglycoside antibiotics and the antineoplastic agent cisplatin. Exposure to aminoglycosides results in hair cell death that is mediated by specific apoptotic proteins, including c-Jun N-terminal kinase (JNK) and caspases. Induction of heat shock proteins (Hsps) can inhibit JNK-and caspase-dependent apoptosis in a variety of systems. We have previously shown that heat shock results in robust upregulation of Hsps in the hair cells of the adult mouse utricle in vitro. In addition, heat shock results in significant inhibition of both cisplatin-and aminoglycoside-induced hair cell death. In this system, Hsp70 is the most strongly induced Hsp, which is upregulated over 250-fold at the level of mRNA 2 h after heat shock. Hsp70 overexpression inhibits aminoglycoside-induced hair cell death in vitro. In this study, we utilized Hsp70-overexpressing mice to determine whether Hsp70 is protective in vivo. Both Hsp70-overexpressing mice and their wildtype littermates were treated with systemic kanamycin (700 mg/kg body weight) twice daily for 14 days. While kanamycin treatment resulted in significant hearing loss and hair cell death in wild-type mice, Hsp70-overexpressing mice were significantly protected against aminoglycosideinduced hearing loss and hair cell death. These data indicate that Hsp70 is protective against aminoglycoside-induced ototoxicity in vivo.

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Apoptosis of guinea pig cochlear hair cells following chronic aminoglycoside treatment

Cited by 66 publications

References 16 publications

Cell Division and Maintenance of Epithelial Integrity in the Deafened Auditory Epithelium

Cell Division and Maintenance of Epithelial Integrity in the Deafened Auditory Epithelium

Caspase-independent pathways of hair cell death induced by kanamycin in vivo

Hsp70 inhibits aminoglycoside-induced hearing loss and cochlear hair cell death

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