title: Simultaneous cell death and upregulation of poly(ADP-ribose) polymerase-1 expression in early postnatal mouse retina.
abstract: OBJECTIVE
  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.
authors.affiliation: Departamento de Biología Celular, Facultad de Ciencias, Universidad de Granada, Granada, Spain. dmoliva@ugr.es
authors.forename: David
authors.initials: D
authors.lastname: Martín-Oliva
authors.forename: Rosa M
authors.initials: RM
authors.lastname: Ferrer-Martín
authors.forename: Ana M
authors.initials: AM
authors.lastname: Santos
authors.forename: M Carmen
authors.initials: MC
authors.lastname: Carrasco
authors.forename: Ana
authors.initials: A
authors.lastname: Sierra
authors.forename: José L
authors.initials: JL
authors.lastname: Marín-Teva
authors.forename: Ruth
authors.initials: R
authors.lastname: Calvente
authors.forename: Julio
authors.initials: J
authors.lastname: Navascués
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Cuadros
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D051033:Apoptosis Inducing Factor / Q000378:metabolism; D015153:Blotting, Western; D004797:Enzyme-Linked Immunosorbent Assay; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology*; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009707:Nucleosomes; D000071137:Poly (ADP-Ribose) Polymerase-1; D011064:Poly Adenosine Diphosphate Ribose / Q000378:metabolism; D011065:Poly(ADP-ribose) Polymerases / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000201:enzymology* / Q000254:growth & development*; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D051033:Apoptosis Inducing Factor; D009707:Nucleosomes; C494830:AIFM1 protein, mouse; D012333:RNA, Messenger; D011064:Poly Adenosine Diphosphate Ribose; C499321:Parp1 protein, mouse; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases