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Calpain and PARP Ac...
Calpain and PARP Activation during Photoreceptor Cell Death in P23H and S334ter Rhodopsin Mutant Rats
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Kaur, Jasvir (author)
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Mencl, Stine (author)
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Sahaboglu, Ayse (author)
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- Farinelli, Pietro (author)
- Lund University,Lunds universitet,Oftalmologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Ophthalmology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine
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- van Veen, Theo (author)
- Lund University,Lunds universitet,Oftalmologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Ophthalmology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine
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Zrenner, Eberhart (author)
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- Ekström, Per (author)
- Lund University,Lunds universitet,Oftalmologi, Lund,Sektion IV,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Ophthalmology, Lund,Section IV,Department of Clinical Sciences, Lund,Faculty of Medicine
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Paquet-Durand, Francois (author)
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Arango-Gonzalez, Blanca (author)
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(creator_code:org_t)
- 2011-07-12
- 2011
- English.
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In: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 6:7
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Abstract
Subject headings
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- Retinitis pigmentosa (RP) is a heterogeneous group of inherited neurodegenerative diseases affecting photoreceptors and causing blindness. Many human cases are caused by mutations in the rhodopsin gene. An important question regarding RP pathology is whether different genetic defects trigger the same or different cell death mechanisms. To answer this question, we analysed photoreceptor degeneration in P23H and S334ter transgenic rats carrying rhodopsin mutations that affect protein folding and sorting respectively. We found strong activation of calpain and poly(ADP-ribose) polymerase (PARP) in both mutants, concomitant with calpastatin down-regulation, increased oxidative DNA damage and accumulation of PAR polymers. These parameters were strictly correlated with the temporal progression of photoreceptor degeneration, mirroring earlier findings in the phosphodiesterase-6 mutant rd1 mouse, and suggesting execution of non-apoptotic cell death mechanisms. Interestingly, activation of caspases-3 and -9 and cytochrome c leakage-key events in apoptotic cell death-were observed only in the S334ter mutant, which also showed increased expression of PARP-1. The identification of the same metabolic markers triggered by different mutations in two different species suggests the existence of common cell death mechanisms, which is a major consideration for any mutation independent treatment.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Oftalmologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Ophthalmology (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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