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PJ34 Protects Photoreceptors from Cell Death by Inhibiting PARP-1 Induced Parthanatos after Experimental Retinal Detachment.

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  • معلومة اضافية
    • المصدر:
      Publisher: Informa Healthcare Country of Publication: England NLM ID: 8104312 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-2202 (Electronic) Linking ISSN: 02713683 NLM ISO Abbreviation: Curr Eye Res Subsets: MEDLINE
    • بيانات النشر:
      Publication: London : Informa Healthcare
      Original Publication: London : IRL Press, [c1981-
    • الموضوع:
      Disease Models, Animal*; Parthanatos/*drug effects ; Phenanthrenes/*pharmacology ; Photoreceptor Cells, Vertebrate/*drug effects ; Poly (ADP-Ribose) Polymerase-1/*antagonists & inhibitors ; Poly(ADP-ribose) Polymerase Inhibitors/*pharmacology ; Retinal Detachment/*prevention & control; Animals ; Apoptosis Inducing Factor/metabolism ; Blotting, Western ; Cell Survival/drug effects ; Male ; Maze Learning/physiology ; Microscopy, Electron, Transmission ; Photoreceptor Cells, Vertebrate/ultrastructure ; Rats ; Rats, Sprague-Dawley ; Reactive Oxygen Species/metabolism ; Retinal Detachment/physiopathology
    • نبذة مختصرة :
      Purpose: Our previous study discoveredreactive oxygen species (ROS) and apoptosis inducing factor (AIF) increased after retinal detachment. Parthanatos is a cell death form involving ROS and AIF, which is induced by poly (ADP-ribose) polymerase-1 (PARP-1). Therefore, we investigated whether PJ34 (a PARP-1 inhibitor) could inhibit parthanatos and protect the photoreceptors from cell death after retinal detachment (RD).
      Methods: Experimental retinal detachment modelswere created in Sprague-Dawley rats by subretinal injection of sodium hyaluronate.PJ34 orDMSO were introduced into subretinal space at RD induction, respectively. The structure of retinas and the morphology of photoreceptors were observed by hematoxylin eosin (H&E) staining and transmission electron microscope (TEM). Parthanatos related proteins (PARP-1, PAR,AIF) were detected by Western blot. The vision-dependent behavior of rat was tested by Morris water maze.
      Results: H&E staining and TEM results indicated that the structure and outer nuclear layer (ONL) thickness of retinas were preserved, and the photoreceptors death decreasedwith PJ34 treatment. Western blot showed that the expression of PARP-1, PAR and AIF were decreased withPJ34 treatment. In addition, administration of PJ34 also improved the vision-dependent behavior of rat.
      Conclusions: These findings suggested that PJ34 is a potential therapeutic agent that attenuated photoreceptor parthanatos death in retinal detachment through inhibition of PARP-1/AIF pathway.
    • Contributed Indexing:
      Keywords: PJ34; Retinal detachment; parthanatos; photoreceptors; poly (ADP-ribose) polymerase-1
    • الرقم المعرف:
      0 (Apoptosis Inducing Factor)
      0 (N-(oxo-5,6-dihydrophenanthridin-2-yl)-N,N-dimethylacetamide hydrochloride)
      0 (Phenanthrenes)
      0 (Poly(ADP-ribose) Polymerase Inhibitors)
      0 (Reactive Oxygen Species)
      EC 2.4.2.30 (Parp1 protein, rat)
      EC 2.4.2.30 (Poly (ADP-Ribose) Polymerase-1)
    • الموضوع:
      Date Created: 20200602 Date Completed: 20211111 Latest Revision: 20211111
    • الموضوع:
      20231215
    • الرقم المعرف:
      10.1080/02713683.2020.1776881
    • الرقم المعرف:
      32478624