Heat shock protein 70 (HSP70) is critical for the photoreceptor stress response after retinal detachment via modulating anti-apoptotic Akt kinase

Maki Kayama, Toru Nakazawa, Aristomenis Thanos, Yuki Morizane, Yusuke Murakami, Sofia Theodoropoulou, Toshiaki Abe, Demetrios Vavvas, Joan W. Miller

Research output: Contribution to journalArticle

35 Citations (Scopus)

Abstract

Photoreceptor apoptosis is a major cause of vision loss in many ocular diseases. Significant progress has been made to elucidate the molecular pathways involved in this process, yet little is known about proteins counteracting these apoptotic pathways. It is established that heat shock proteins (HSPs) function as molecular helper proteins (chaperones) by preventing protein aggregation and facilitating refolding of dysfunctional proteins, critical to the survival of all organisms. Here, we investigated the role of HSP70 on photoreceptor survival after experimental retinal detachment (RD) in mice and rats. We found that HSP70 was up-regulated after RD and associated with phosphorylated Akt, thereby preventing its dephosphorylation and further activation of cell death pathways. Administration of quercetin, which inhibits HSP70 and suppresses Akt phosphorylation significantly increased photoreceptor apoptosis. Similarly, RD-induced photoreceptor apoptosis was augmented in mice carrying hypomorphic mutations of the genes encoding HSP70. On the other hand, administration of geranylgeranylacetone, which induces an increase in HSP70 significantly decreased photoreceptor apoptosis after RD through prolonged activation of Akt pathway. Thus, HSP70 may be a favorable potential target to increase photoreceptor cell survival after RD.

Original languageEnglish
Pages (from-to)1080-1091
Number of pages12
JournalAmerican Journal of Pathology
Volume178
Issue number3
DOIs
Publication statusPublished - Mar 2011

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HSP70 Heat-Shock Proteins
Retinal Detachment
Phosphotransferases
Apoptosis
geranylgeranylacetone
Protein Refolding
Photoreceptor Cells
Proteins
Eye Diseases
Quercetin
Heat-Shock Proteins
Cell Survival
Cell Death
Phosphorylation
Mutation
Genes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Heat shock protein 70 (HSP70) is critical for the photoreceptor stress response after retinal detachment via modulating anti-apoptotic Akt kinase. / Kayama, Maki; Nakazawa, Toru; Thanos, Aristomenis; Morizane, Yuki; Murakami, Yusuke; Theodoropoulou, Sofia; Abe, Toshiaki; Vavvas, Demetrios; Miller, Joan W.

In: American Journal of Pathology, Vol. 178, No. 3, 03.2011, p. 1080-1091.

Research output: Contribution to journalArticle

Kayama, Maki ; Nakazawa, Toru ; Thanos, Aristomenis ; Morizane, Yuki ; Murakami, Yusuke ; Theodoropoulou, Sofia ; Abe, Toshiaki ; Vavvas, Demetrios ; Miller, Joan W. / Heat shock protein 70 (HSP70) is critical for the photoreceptor stress response after retinal detachment via modulating anti-apoptotic Akt kinase. In: American Journal of Pathology. 2011 ; Vol. 178, No. 3. pp. 1080-1091.
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