Hostname: page-component-5db58dd55d-ggg9q Total loading time: 0 Render date: 2026-05-25T15:51:27.203Z Has data issue: false hasContentIssue false
  • English
  • Français

Heat shock protein 70 and cellular disturbances in cochlear cisplatin ototoxicity model

Published online by Cambridge University Press:  23 March 2010

J R García-Berrocal ,
J Nevado ,
J Á González-García ,
C Sánchez-Rodríguez ,
R Sanz ,
A Trinidad ,
P España ,
M J Citores  and
R Ramírez-Camacho
J R García-Berrocal*
Affiliation:
Department of Otorhinolaryngology, Hospital Universitario Puerta de Hierro, Madrid, Spain
J Nevado
Affiliation:
Instituto de Genética Médica y Molecular, Hospital Universitario La Paz, Madrid, Spain Centro de Investigación Biomédica en Red de Enfermedades Raras, Madrid, Spain
J Á González-García
Affiliation:
Department of Otorhinolaryngology, Hospital Universitario Puerta de Hierro, Madrid, Spain
C Sánchez-Rodríguez
Affiliation:
Department of Otorhinolaryngology and Research Unit, Hospital Universitario de Getafe, Madrid, Spain
R Sanz
Affiliation:
Department of Otorhinolaryngology and Research Unit, Hospital Universitario de Getafe, Madrid, Spain
A Trinidad
Affiliation:
Department of Otorhinolaryngology, Hospital Universitario Puerta de Hierro, Madrid, Spain
P España
Affiliation:
Department of Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain
M J Citores
Affiliation:
Department of Internal Medicine, Hospital Universitario Puerta de Hierro, Madrid, Spain
R Ramírez-Camacho
Affiliation:
Department of Otorhinolaryngology, Hospital Universitario Puerta de Hierro, Madrid, Spain
*
Address for correspondence: Dr José Ramón García-Berrocal, Servicio de Otorrinolaringología, Hospital Universitario Puerta de Hierro-Majadahonda, Manuel de Falla 1, 28222 Majadahonda, Madrid, Spain. Fax: +34 91 3730535 E-mail: jrgarciab@yahoo.com
Get access Rights & Permissions [Opens in a new window]

Abstract

Background:

Exposure to cisplatin leads to cochlear cell death by apoptosis; these changes are most marked on the seventh day after exposure. Heat shock proteins are induced in inner ear cells in response to a variety of stimuli. This study examined the role of heat shock protein 70 in cisplatin-induced cochlear cell death.

Methods:

Fifty-six Sprague–Dawley rats were involved. Some were injected with cisplatin (5 mg/kg body weight), some with cisplatin plus the caspase inhibitor Z-Asp(OMe)-Glu(OMe)-Val-Asp(OME)-fluoromethylketone (5 mg/kg body weight) and others were left as controls (being injected only with saline). Seven days later, we examined the expression of heat shock protein 70 and several other apoptosis-related proteins within the rat cochlear cells; we also assessed total superoxide dismutase activity, auditory brainstem response and auditory steady state response.

Results:

Seven days after cisplatin injection, significantly increased expression of heat shock protein 70 was found within the rat cochleae. This correlated with increased executioner caspase levels, total superoxide dismutase activity and auditory brainstem response thresholds, and a significant elevation in auditory steady state response thresholds. Inhibition of caspase-3 activity significantly reduced cochlear heat shock protein 70 expression and total superoxide dismutase activity, and improved auditory brainstem response and auditory steady state response thresholds.

Conclusions:

Seven days after cisplatin exposure, we found disturbances of the cochlear cellular machinery involving heat shock protein 70, other apoptotic proteins and total superoxide dismutase.

Keywords

Cis-platinumOtotoxicityCochlea

Information

Type
Main Articles
Information
The Journal of Laryngology & Otology , Volume 124 , Issue 6 , June 2010 , pp. 599 - 609
Copyright
Copyright © JLO (1984) Limited 2010

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Article purchase

Temporarily unavailable

References

1 Morimoto, RI, Tissieres, A, Georgopoulus, C. Progress and perspectives on the biology of heat shock proteins and molecular chaperones. In: Morimoto, RI, Tissieres, A, Georgopoulus, C, eds. The Biology of Heat Shock Proteins and Molecular Chaperones. Cold Spring Harbor Laboratory Press: New York, 1994;1–30Google Scholar
2 Langer, T, Neupert, W. Heat shock proteins hsp60 and hsp70: their roles in folding, assembly, and membrane translocations of proteins. Curr Top Microbiol Immunol 1991;167:3–30Google ScholarPubMed
3 García-Berrocal, JR, Ramírez-Camacho, R, Arellano, B, Vargas, JA. Validity of the Western blot immunoassay for heat shock protein 70 in associated and isolated immunorelated inner ear disease. Laryngoscope 2002;112:304–9CrossRefGoogle ScholarPubMed
4 Ramírez-Camacho, R, Citores, MJ, Trinidad, A, Verdaguer, JM, García-Berrocal, JR, Marero, AM et al. HSP-70 as a nonspecific early marker in cisplatin ototoxicity. Acta Otolaryngol 2007;127:564–7CrossRefGoogle ScholarPubMed
5 Rybak, LP, Whitworth, CA, Mukherjea, D, Ramkumar, V. Mechanisms of cisplatin-induced ototoxicity and prevention. Hear Res 2007;226:157–67CrossRefGoogle ScholarPubMed
6 Banfi, B, Malgrange, B, Knisz, J, Steger, K, Dubois-Dauphin, M, Crause, KH. Nox3, a superoxide-generating NADPH oxidase of the inner ear. J Biol Chem 2004;277:39739–48Google Scholar
7 Ashkenazi, A, Dixit, VM. Death receptors: signalling and modulation. Science 1998;281:1305–8CrossRefGoogle ScholarPubMed
8 Harris, MH, Thompson, CB. The role of Bcl-2 family in the regulation of outer mitochondrial membrane permeability. Cell Death Differ 2000;7:1182–91CrossRefGoogle ScholarPubMed
9 García-Berrocal, JR, Nevado, J, Ramírez-Camacho, R, Sanz, R, González-García, JA, Sanchez-Rodríguez, C et al. The anticancer drug cisplatin induces an intrinsic apoptotic pathway inside the inner ear. Br J Pharmacol 2007;152:1012–20CrossRefGoogle ScholarPubMed
10 Thornberry, NA, Chapman, KT, Nicholson, DW. Determination of caspase specificities using a peptide combinatorial library. Meth Enzymol 2000;322:100–10CrossRefGoogle ScholarPubMed
11 Nevado, J, Sanz, R, Casqueiro, JC, Ayala, A, García-Berrocal, JR, Ramirez-Camacho, R. Ageing evokes an intrinsic pro-apoptotic signalling pathway in rat cochlea. Acta Otolaryngol 2006;126:1134–9CrossRefGoogle ScholarPubMed
12 Lee, JE, Nagakawa, T, Kita, T, Kim, TS, Iguchi, F, Endo, T et al. Mechanisms of apoptosis induced by cisplatin in marginal cells in mouse stria vascularis. ORL J Otorhinolaryngol Relat Spec 2004;66:111–18CrossRefGoogle ScholarPubMed
13 Sreedhar, AS, Csermely, P. Heat shock proteins in the regulation of apoptosis: new strategies in tumor therapy: a comprehensive review. Pharmacol Ther 2004;101:227–57CrossRefGoogle ScholarPubMed
14 Oh, SH, Yu, WSY, Song, B-H, Lim, D, Koo, JW, Chang, SO et al. Expression of heat shock protein 72 in rat cochlea with cisplatin-induced acute ototoxicity. Acta Otolaryngol 2000;120:146–50Google ScholarPubMed
15 Cunningham, LL, Brandon, CS. Heat shock inhibits both aminoglycoside and cisplatin induced sensory hair cell death. J Assoc Res Otolaryngol 2006;7:299–307CrossRefGoogle ScholarPubMed
16 Martindale, JL, Holbrook, NJ. Cellular response to oxidative stress: signalling for suicide and survival. J Cell Physiol 2002;192:1–15CrossRefGoogle ScholarPubMed
17 Dechesne, CJ, Kim, HN, Nowak, TS Jr, Wenthold, RJ. Expression of heat shock protein, HSP72, in the guinea pig and rat cochlea after hyperthermia: immunochemical and in situ hybridization analysis. Hear Res 1992;59:195–204CrossRefGoogle ScholarPubMed
18 Lim, HH, Jenkins, OH, Myers, MW, Miller, JM, Altschuler, RA. Detection of HSP 72 synthesis after acoustic overstimulation in rat cochlea. Hear Res 1993;104:181–8Google Scholar
19 Esteban-Fernandez, D, Gómez-Gómez, MM, Cañas, B, Verdaguer, JM, Ramirez, R, Palacios, MA. Speciation analysis of platinum antitumoral drugs in impacted tissues. Talanta 2007;72:768–73CrossRefGoogle ScholarPubMed
20 Taleb, M, Brandon, CS, Lee, FS, Lomax, MI, Dillmann, WH, Cunningham, LL. Hsp70 inhibits aminoglycoside-induced hair cell death and is necessary for the protective effect of heat shock. J Assoc Res Otolaryngol 2008;9:277–89CrossRefGoogle ScholarPubMed
21 Boettcher, FA, Spongr, VP, Salvi, RJ. Physiological and histological changes associated with the reduction in threshold shift during interrupted noise exposure. Hear Res 1992;62:217–36CrossRefGoogle ScholarPubMed
22 Wang, J, Ladrech, S, Pujol, R, Brabet, P, Van de Water, TR, Puel, JL. Caspase inhibitors, but not c-jun NH2-terminal kinase inhibitor treatment prevent cisplatin-induced hearing loss. Cancer Res 2004;64:9217–24CrossRefGoogle Scholar
23 Gower, VC, Thompson, AM. Localization of inducible heat shock protein mRNA in the guinea pig cochlea with a nonradioactive in situ hybridization technique. Laryngoscope 1997;107:228–32CrossRefGoogle ScholarPubMed
24 Aghdassi, A, Pillips, P, Dudeja, V, Dhaulakhandi, D, Sharif, R, Dawra, R et al. Heat shock protein 70 increases tumorigenicity and inhibits apoptosis in pancreatic adenocarcinoma. Cancer Res 2007;67:616–25CrossRefGoogle ScholarPubMed
25 Phillips, PA, Dudeja, V, McCarroll, JA, Borja-Cacho, D, Dawra, RK, Grizzle, WE et al. Triptolide induces pancreatic cancer cell death via inhibition of heat shock protein. Cancer Res 2007;67:9407–16CrossRefGoogle ScholarPubMed
26 Estrem, SA, Babin, RW, Ryu, JH, Moore, KC. Cis-diamminedichloroplatinum (II) ototoxicity in the guinea pig. Otolaryngol Head Neck Surg 1981;89:638–45CrossRefGoogle ScholarPubMed
27 Anniko, M, Sobin, A. Cisplatin: evaluation of its ototoxic potential. Am J Otolaryngol 1986;7:276–93CrossRefGoogle ScholarPubMed
28 Watanabe, K, Yagi, T. Expression of myeloperoxidase in the inner ear of cisplatin-treated guinea pigs. Anticancer Drugs 2000;11:27–30CrossRefGoogle ScholarPubMed
29 Ramírez-Camacho, R, García-Berrocal, JR, Buján, J, Martin-Marero, A, Trinidad, A. Supporting cells as a target of cisplatin-induced inner ear damage: therapeutic implications. Laryngoscope 2006;114:533–7CrossRefGoogle Scholar
30 Ramírez-Camacho, R, García-Berrocal, JR, Trinidad, A, González-García, JA, Verdaguer, JM, Ibáñez, A et al. Central role of supporting cells in cochlear homeostasis and pathology. Med Hypotheses 2004;67:550–5CrossRefGoogle Scholar