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Selective photoreceptor loss can be induced in mice by an intraperitoneal injection of <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea (<jats:styled-content style=\"fixed-case\">MNU<\/jats:styled-content>) and, because of its selectivity, this model is widely used to study the mechanism of <jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content>s. Although it is known that calcium\u2010calpain activation and lipid peroxidation are involved in the initiation of cell death, the precise mechanisms of this process remain unknown. Heat shock protein 70 (<jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>70) has been shown to function as a chaperone molecule to protect cells against environmental and physiological stresses. In this study, we investigated the role of <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>70 on photoreceptor cell death in mice. <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>70 induction by valproic acid, a histone deacetylase inhibitor, attenuated the photoreceptor cell death by <jats:styled-content style=\"fixed-case\">MNU<\/jats:styled-content> through inhibition of apoptotic caspase signals. Furthermore, <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>70 itself was rapidly and calpain\u2010dependently cleaved after <jats:styled-content style=\"fixed-case\">MNU<\/jats:styled-content> treatment. Therefore, <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>70 induction by valproic acid was dually effective against <jats:styled-content style=\"fixed-case\">MNU<\/jats:styled-content>\u2010induced photoreceptor cell loss as a result of its anti\u2010apoptotic actions and its ability to prevent <jats:styled-content style=\"fixed-case\">HSP<\/jats:styled-content>70 degradation. These findings might help lead us to a better understanding of the pathogenic mechanism of <jats:styled-content style=\"fixed-case\">RD<\/jats:styled-content>s.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc12750-fig-0008-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Retinal degenerative diseases are characterized by the loss of photoreceptor cells. We proposed the following cascade for <jats:italic>N<\/jats:italic>\u2010methyl\u2010<jats:italic>N<\/jats:italic>\u2010nitrosourea (MNU)\u2010induced photoreceptor cell death: MNU gives rise to cleavage of heat shock protein 70 (HSP70); HSP70 induction by valproic acid (VPA) is dually effective against MNU\u2010induced photoreceptor cell loss because of its anti\u2010apoptotic actions and its ability to prevent HSP70 degradation. We hope that the present study heralds a new era in developing therapeutic tools against retinal degenerative diseases.<\/jats:p>","DOI":"10.1111\/jnc.12750","type":"journal-article","created":{"date-parts":[[2014,4,29]],"date-time":"2014-04-29T09:59:00Z","timestamp":1398765540000},"page":"707-719","source":"Crossref","is-referenced-by-count":29,"title":["Heat shock protein 70 induction by valproic acid delays photoreceptor cell death by <i>N<\/i>\u2010methyl\u2010<i>N<\/i>\u2010nitrosourea in mice"],"prefix":"10.1111","volume":"130","author":[{"given":"Yoshiki","family":"Koriyama","sequence":"first","affiliation":[{"name":"Department of Molecular Neurobiology Graduate School of Medicine Kanazawa University Kanazawa Japan"},{"name":"Graduate School and Faculty of Pharmaceutical Sciences Suzuka University of Medical Science Suzuka Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kayo","family":"Sugitani","sequence":"additional","affiliation":[{"name":"Division of 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