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Publication : Simultaneous cell death and upregulation of poly(ADP-ribose) polymerase-1 expression in early postnatal mouse retina.

First Author  Martín-Oliva D Year  2011
Journal  Invest Ophthalmol Vis Sci Volume  52
Issue  10 Pages  7445-54
PubMed ID  21705688 Mgi Jnum  J:181599
Mgi Id  MGI:5312013 Doi  10.1167/iovs.11-7222
Citation  Martin-Oliva D, et al. (2011) Simultaneous cell death and upregulation of poly(ADP-ribose) polymerase-1 expression in early postnatal mouse retina. Invest Ophthalmol Vis Sci 52(10):7445-54
abstractText  PURPOSE: Poly(ADP-ribose) polymerase (PARP)-1 is a nuclear enzyme that transfers ADP-ribose units (PAR polymer) to nuclear proteins and has been implicated in caspase-independent cell death in different models of retinal degeneration. The involvement of PARP-1 in cell death occurring during normal postnatal development of the mouse retina was investigated. In addition, the expression of apoptosis-inducing factor (AIF), a caspase-independent cell death mediator, was explored because PARP-1 activation has been related to the translocation of a 57-kDa form of AIF into the cell nucleus. METHODS: Cell death was determined in retinas of developing mice by both ELISA and TUNEL. PARP-1, PAR, and AIF were analyzed by immunocytochemistry and immunoblotting. Quantification of PARP-1 mRNA levels was also performed by real-time PCR. RESULTS: PARP-1 upregulation and PAR polymer formation, indicative of PARP-1 activity, were observed during the first postnatal week simultaneously with the presence of abundant dying cells, some of which were not associated with active caspase-3. PARP-1 was downregulated and PARP-1 activity progressively declined in the retina during subsequent postnatal development, coinciding with the decrease in cell death. Truncated AIF (57 kDa) was present in the retina during the first postnatal week, gradually decreasing thereafter, and had a nuclear localization in some cells, which also showed strong PAR polymer nuclear staining. CONCLUSIONS: These results show that a caspase-independent cell death pathway exists during the normal development of the mouse retina and suggest that PARP-1 participates in this cell death pathway by mediating AIF translocation to the cell nucleus.
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