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Heat shock protein 70 induction by valproic acid delays photoreceptor cell death by N ‐methyl‐ N ‐nitrosourea in mice
Author(s) -
Koriyama Yoshiki,
Sugitani Kayo,
Ogai Kazuhiro,
Kato Satoru
Publication year - 2014
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.12750
Subject(s) - photoreceptor cell , programmed cell death , heat shock protein , apoptosis , microbiology and biotechnology , valproic acid , hsp70 , chemistry , calpain , retinal degeneration , retinal , biochemistry , biology , epilepsy , neuroscience , gene , enzyme
Retinal degenerative diseases ( RD s) are a group of inherited diseases characterized by the loss of photoreceptor cells. Selective photoreceptor loss can be induced in mice by an intraperitoneal injection of N ‐methyl‐ N ‐nitrosourea ( MNU ) and, because of its selectivity, this model is widely used to study the mechanism of RD s. Although it is known that calcium‐calpain activation and lipid peroxidation are involved in the initiation of cell death, the precise mechanisms of this process remain unknown. Heat shock protein 70 ( HSP 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 HSP 70 on photoreceptor cell death in mice. HSP 70 induction by valproic acid, a histone deacetylase inhibitor, attenuated the photoreceptor cell death by MNU through inhibition of apoptotic caspase signals. Furthermore, HSP 70 itself was rapidly and calpain‐dependently cleaved after MNU treatment. Therefore, HSP 70 induction by valproic acid was dually effective against MNU ‐induced photoreceptor cell loss as a result of its anti‐apoptotic actions and its ability to prevent HSP 70 degradation. These findings might help lead us to a better understanding of the pathogenic mechanism of RD s.Retinal degenerative diseases are characterized by the loss of photoreceptor cells. We proposed the following cascade for N ‐methyl‐ N ‐nitrosourea (MNU)‐induced 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‐induced photoreceptor cell loss because of its anti‐apoptotic 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.