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Geldanamycin activates Hsp70 response and attenuates okadaic acid-induced cytotoxicity in human retinal pigment epithelial cells.
Department of Ophthalmology, University of Kuopio, Kuopio, Finland; Department of Ophthalmology, Kuopio University Hospital, Kuopio, Finland.
Department of Ophthalmology, University of Kuopio, Kuopio, Finland.
Department of Anatomy, University of Kuopio, Kuopio, Finland.
Department of Neuroscience and Neurology, University of Kuopio, Kuopio, Finland.
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2005 (English)In: Brain Research. Molecular Brain Research, ISSN 0169-328X, E-ISSN 1872-6941, Vol. 137, no 1-2, 126-131 p., 15950770Article in journal (Refereed) Published
Abstract [en]

Reversible protein phosphorylation regulates the biological activities of many human proteins involved in crucial cellular processes, e.g., protein-protein interactions, cell signaling, gene transcription, cell growth, and death. A malfunction of cellular homeostasis in retinal pigment epithelial (RPE) cells is involved in the age-related retinal degeneration. In this study, we examined cytotoxicity in human RPE cells subjected to the protein phosphatase inhibitor, okadaic acid (OA). Moreover, the influence of Hsp90 inhibitor geldanamycin (GA), a benzoquinone ansamycin, in cytoprotection was assessed. Hsp70 protein levels were analyzed by Western blot. Cellular viability was determined by LDH and MTT assays. To study apoptotic cell death, caspase-3 enzyme activity was measured by assaying the cleavage of a fluorescent peptide substrate and Hoechst dye was used to visualize nuclear morphology. OA treatment caused morphological changes and induced cytotoxicity by caspase-3-independent manner in the RPE cells. No evidence of nuclear fragmentation was observed in response to OA. Interestingly, GA treatment accumulated Hsp70 protein and attenuated OA-induced cytotoxicity. This study suggests that Hsp70 and Hsp90 are closely related to cytoprotection of RPE cells in response to protein phosphatase inhibition.

Place, publisher, year, edition, pages
Elsevier, 2005. Vol. 137, no 1-2, 126-131 p., 15950770
Keyword [en]
Opthalmology, retinal pigment epithelial cells, geldanamycin, heat shock protein, cell viability
National Category
Cell and Molecular Biology Biochemistry and Molecular Biology Ophthalmology
Research subject
Biochemistry; cellforskning; Ophtalmology
URN: urn:nbn:se:umu:diva-106656DOI: 10.1016/j.molbrainres.2005.02.027PubMedID: 15950770OAI: diva2:843222
Available from: 2015-07-27 Created: 2015-07-27 Last updated: 2015-07-27

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