Abstract
Retinitis pigmentosa is a disease characterized by the loss of photoreceptor cells. The N-methyl-N-nitrosourea (MNU)-induced retinal degeneration model is widely used to study the mechanism of these retinal degenerative disorders because of its selective photoreceptor cell death. As for the cell death mechanism of MNU, calcium-calpain activation and lipid peroxidation processes are involved in the initiation of this cell death. Although such molecular mechanisms of the MNU-induced cell death have been described, the total image of the cell death is still obscure. Heat shock protein 70 (HSP70) has been shown to function as a chaperon molecule to protect cells against environmental and physiological stresses. In this study, we investigated the effect of geranylgeranylacetone (GGA), an accylic polyisoprenoid, on MNU-induced photoreceptor cell loss. HSP70 induction by GGA was effective against MNU-induced photoreceptor cell loss as a result of its ability to prevent HSP70 degradation. The data indicate that GGA may help to suppress the onset and progression of retinitis pigmentosa.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsReferences
Caprioli J, Ishii Y, Kwong JM (2003) Retinal ganglion cell protection with geranylgeranylacetone, a heat shock protein inducer, in a rat glaucoma model. Trans Am Ophthalmol Soc 101:39–50
Fliesler SJ et al (1983) Chemistry and metabolism of lipids in the vertebrate retina. Prog Lipid Res 22:79–131
Garrido C, Schmitt E, Candé C et al (2003) HSP27 and HSP70: potentially oncogenic apoptosis inhibitors. Cell Cycle 2:579–584
Kayama M, Nakazawa T, Thanos A et al (2011) Heat shock protein 70 (HSP70) is critical for the photoreceptor stress response after retinal detachment via modulating anti-apoptotic Akt kinase. Am J Pathol 178:1080–1091
Koriyama Y, Nakayama Y, Matsugo S et al (2013a) Protective effect of lipoic acid against oxidative stress is mediated by Keap1/Nrf2-dependent heme oxygenase-1 induction in the RGC-5 cell line. Brain Res 1499:145–157
Koriyama Y, Takagi Y, Chiba K et al (2013b) Requirement of retinoic acid receptor β for genipin derivative-induced optic nerve regeneration in adult rat retina. PLoS One 8:e71252
Koriyama Y, Sugitani K, Ogai K et al (2014) Heat shock protein 70 induction by valproic acid delays photoreceptor cell death by N-methyl-N-nitrosourea in mice. J Neurochem 130:707–719
Nagar S, Krishnamoorthy V, Cherukuri P et al (2009) Early remodeling in an inducible animal model of retinal degeneration. Neuroscience 160:517–529
Oka T, Nakajima T, Tamada Y et al (2007) Contribution of calpains to photoreceptor cell death in N-methyl-N-nitrosourea-treated rats. Exp Neurol 204:39–48
Tsubura A, Yoshizawa K, Kuwata M et al (2010) Animal models for retinitis pigmentosa induced by MNU; disease progression, mechanisms and therapeutic trials. Histol Histopathol 25:933–944
Tsubura A, Lai YC, Miki H et al (2011) Animal models of N-Methyl-N-nitrosourea-induced mammary cancer and retinal degeneration with special emphasis on therapeutic trials. In Vivo25:11–22
Tsuruma K, Yamauchi M, Inokuchi Y et al (2012) Role of oxidative stress in retinal photoreceptor cell death in N-methyl-N-nitrosourea-treated mice. J Pharmacol Sci 118:51–62
Yamashima T (2012) Hsp70.1 and related lysosomal factors for necrotic neuronal death. J Neurochem 120:477–494
Yoshizawa K, Yang J, Senzaki H et al (2000) Caspase-3 inhibitor rescues N-methyl-N-nitrosourea-induced retinal degeneration in Sprague-Dawley rats. Exp Eye Res 71:629–635
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2016 Springer International Publishing Switzerland
About this paper
Cite this paper
Koriyama, Y., Ogai, K., Sugitani, K., Hisano, S., Kato, S. (2016). Geranylgeranylacetone Suppresses N-Methyl-N-nitrosourea-Induced Photoreceptor Cell Loss in Mice. In: Bowes Rickman, C., LaVail, M., Anderson, R., Grimm, C., Hollyfield, J., Ash, J. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 854. Springer, Cham. https://doi.org/10.1007/978-3-319-17121-0_32
Download citation
DOI: https://doi.org/10.1007/978-3-319-17121-0_32
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-17120-3
Online ISBN: 978-3-319-17121-0
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)