A role of Heat Shock Protein 70 in Photoreceptor Cell Death: Potential as a Novel Therapeutic Target in Retinal Degeneration.
Retinal degenerative diseases (RDs) such as retinitis pigmentosa (RP) are a genetically heterogeneous group of disorders characterized by night blindness and peripheral vision loss, which caused by the dysfunction and death of photoreceptor cells. Although many causative gene mutations have been reported, the final common end stage is photoreceptor cell death. Unfortunately, no effective treatments or therapeutic agents have been discovered. Heat shock protein 70 (HSP70) is highly conserved and has antiapoptotic activities. A few reports have shown that HSP70 plays a role in RDs. Thus, we focused on the role of HSP70 in photoreceptor cell death. Using the N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell death model in mice, we could examine two stages of the novel cell death mechanism; the early stage, including HSP70 cleavage through protein carbonylation by production of reactive oxygen species, lipid peroxidation and Ca(2+) influx/calpain activation, and the late stage of cathepsin and/or caspase activation. The upregulation of intact HSP70 expression by its inducer is likely to protect photoreceptor cells. In this review, we focus on the role of HSP70 and the novel cell death signaling process in RDs. We also describe candidate therapeutic agents for RDs.
Graduate School and Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Japan.
Ayako
A
Furukawa
Graduate School and Faculty of Pharmaceutical Sciences, Suzuka University of Medical Science, Suzuka, Japan.
Yoshiki
Y
Koriyama
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D020419:Photoreceptor Cells, Vertebrate / Q000187:drug effects / Q000378:metabolism*; D012162:Retinal Degeneration / Q000188:drug therapy / Q000378:metabolism*
D018840:HSP70 Heat-Shock Proteins
HSP70 heat shock proteins; Photoreceptor; Protein carbonylation; Retina; Retinitis pigmentosa