Calpain and PARP Activation during Photoreceptor Cell Death in P23H and S334ter Rhodopsin Mutant Rats
(2011) In PLoS ONE 6(7).- Abstract
- 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... (More)
- 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. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2092871
- author
- Kaur, Jasvir ; Mencl, Stine ; Sahaboglu, Ayse ; Farinelli, Pietro LU ; van Veen, Theo LU ; Zrenner, Eberhart ; Ekström, Per LU ; Paquet-Durand, Francois and Arango-Gonzalez, Blanca
- organization
- publishing date
- 2011
- type
- Contribution to journal
- publication status
- published
- subject
- in
- PLoS ONE
- volume
- 6
- issue
- 7
- publisher
- Public Library of Science (PLoS)
- external identifiers
-
- wos:000292699000027
- scopus:79960192809
- pmid:21765948
- ISSN
- 1932-6203
- DOI
- 10.1371/journal.pone.0022181
- language
- English
- LU publication?
- yes
- id
- 6ac07996-da12-444b-8004-5fa882cb0a70 (old id 2092871)
- date added to LUP
- 2016-04-01 13:33:22
- date last changed
- 2022-03-06 06:27:36
@article{6ac07996-da12-444b-8004-5fa882cb0a70, abstract = {{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.}}, author = {{Kaur, Jasvir and Mencl, Stine and Sahaboglu, Ayse and Farinelli, Pietro and van Veen, Theo and Zrenner, Eberhart and Ekström, Per and Paquet-Durand, Francois and Arango-Gonzalez, Blanca}}, issn = {{1932-6203}}, language = {{eng}}, number = {{7}}, publisher = {{Public Library of Science (PLoS)}}, series = {{PLoS ONE}}, title = {{Calpain and PARP Activation during Photoreceptor Cell Death in P23H and S334ter Rhodopsin Mutant Rats}}, url = {{https://lup.lub.lu.se/search/files/3445462/2221685.pdf}}, doi = {{10.1371/journal.pone.0022181}}, volume = {{6}}, year = {{2011}}, }