Expression of Insulin-like Growth Factors in a Mouse Model of Salicylate Ototoxicity
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Objectives. Insulin-like growth factors (IGFs) are known to be neurotrophic factors, and they efficiently signal to cells to grow, differentiate and survive. The purpose of study was to identify the expressions of IGFs in mice with salicylate ototoxicity, which is a typical reversible hearing loss model. Methods. The mice were given intraperitoneal injections of salicylate (400 mg/kg) and about a 30 dB threshold shift was achieved at 3 hours. The expressions of IGF-1 and 2 were confirmed by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Localization of IGFs was confirmed using confocal immunofluorescence imaging. For in-vitro study on the HEI-OC1 auditory cells, the cell viability was calculated and the apoptotic features of the nuclei were observed with Hoechst staining. Results. The expressions of the IGFs mRNA and protein were significantly increased in the salicylate ototoxicity groups compared with that of the normal control group. Salicylate induced apoptosis and decreased viability of the HEI-OC1auditory cells in a time- and dose-dependent manner. The expressions of IGFs were localized in the stria vascularis,and these IGFs play a protective role in the in-vivo condition of salicylate ototoxicity. Conclusion. IGFs were highly expressed in the mice with salicylate ototoxicity, and this expression was mainly focused in the stria vascularis in the salicylate intoxicated mice. The systemic action of IGFs, which were expressed in the vascular-rich stria vascularis, can act as a major protective mechanism in a mouse model of salicylate ototoxicity.
Abstract
Objectives. Insulin-like growth factors (IGFs) are known to be neurotrophic factors, and they efficiently signal to cells to grow, differentiate and survive. The purpose of study was to identify the expressions of IGFs in mice with salicylate ototoxicity, which is a typical reversible hearing loss model. Methods. The mice were given intraperitoneal injections of salicylate (400 mg/kg) and about a 30 dB threshold shift was achieved at 3 hours. The expressions of IGF-1 and 2 were confirmed by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blotting. Localization of IGFs was confirmed using confocal immunofluorescence imaging. For in-vitro study on the HEI-OC1 auditory cells, the cell viability was calculated and the apoptotic features of the nuclei were observed with Hoechst staining. Results. The expressions of the IGFs mRNA and protein were significantly increased in the salicylate ototoxicity groups compared with that of the normal control group. Salicylate induced apoptosis and decreased viability of the HEI-OC1auditory cells in a time- and dose-dependent manner. The expressions of IGFs were localized in the stria vascularis,and these IGFs play a protective role in the in-vivo condition of salicylate ototoxicity. Conclusion. IGFs were highly expressed in the mice with salicylate ototoxicity, and this expression was mainly focused in the stria vascularis in the salicylate intoxicated mice. The systemic action of IGFs, which were expressed in the vascular-rich stria vascularis, can act as a major protective mechanism in a mouse model of salicylate ototoxicity.
참고문헌 (20)
- Varela-Nieto I, "Trophic effects of insulin-like growth factor- I (IGF-I) in the inner ear", Hear Res, 196(1-2), pp.19~25 (2004)
- Cohen P, "Overview of the IGF-I system", Horm Res, 65(Suppl 1), pp.3~8 (2006)
- Dell SD, "Insulin-like growth factor II (IGF-II)", Int J Biochem Cell Biol, 30(7), pp.767~771 (1998)
- Lauterio TJ, "The effects of IGF-I and IGF-II on cell growth and differentiation in the central nervous system", Adv Exp Med Biol, 321, pp.31~36 (1992)
- Malgrange B, "Identification of factors that maintain mammalian outer hair cells in adult organ of Corti explants", Hear Res, 170(1-2), pp.48~58 (2002)
- Burns JL, "Cell survival and proliferation are modified by insulin-like growth factor 2 between days 9 and 10 of mouse gestation", Development, 128(19), pp.3819~3830 (2001)
- Camarero G, "Delayed inner ear maturation and neuronal loss in postnatal Igf-1-deficient mice", J Neurosci, 21(19), pp.7630~7641 (2001)
- Camarero G, "Cochlear abnormalities in insulin-like growth factor-1 mouse mutants", Hear Res, 170(1-2), pp.2~11 (2002)
- Biddle C, "Insulin-like growth factors and the multiplication of Tera-2, a human teratoma-derived cell line", J Cell Sci, 90(Pt 3), pp.475~484 (1988)
- Ye P, "Myelination is altered in insulin-like growth factor-I null mutant mice", J Neurosci, 22(14), pp.6041~6051 (2002)
- Mori H, "Expression of mouse igf2 mRNA-binding protein 3 and its implications for the developing central nervous system", J Neurosci Res, 64(2), pp.132~43 (2001)
- Dikkes P, "Effect of kainic acid treatment on insulin-like growth factor-2 receptors in the IGF2-deficient adult mouse brain", Brain Res, 1131(1), pp.77~87 (2007)
- Vincent AM, "Control of cell survival by IGF signaling pathways", Growth Horm IGF Res, 12(4), pp.193~197 (2002)
- Leon Y, "Programmed cell death in the development of the vertebrate inner ear", Apoptosis, 9(3), pp.255~264 (2004)
- Staecker H, "Van De Water TR. Factors controlling hair-cell regeneration", repair in the inner ear, 1998, pp.8(4), 480~
- Fortes WM, "End-to-side neurorrhaphy: evaluation of axonal response and upregulation of IGF-I and IGF-II in a non-injury model", J Reconstr Microsurg, 15(6), pp.449~457 (1999)
- Cazals Y, "Auditory sensori-neural alterations induced by salicylate", Prog Neurobiol, 62(6), pp.583~631 (2000)
- Im GJ, "erential gene expression profiles in salicylate ototoxicity of the mouse", Acta Otolaryngol, 127(5), pp.459~469 (2007)
- Kalinec GM, "A cochlear cell line as an in vitro system for drug ototoxicity screening", Audiol Neurootol., 8(4), pp.177~89 (2003)
- 임현우, "Apoptotic Pattern of Cochlear Outer Hair Cells and Frequency-specific Hearing Threshold Shift in Noise-exposed BALB", c Mice, 2008, pp.1(2), 80~85[DOI]