Reduction but not cleavage of poly(ADP-ribose) polymerase during stress-mediated cell death in the rat hippocampus

Neuroreport. 2003 May 23;14(7):935-9. doi: 10.1097/01.wnr.0000074340.81633.f1.

Abstract

Sustained stress induces neuronal atrophy and death, especially in the hippocampus, which impairs hippocampal function. However, underlying mechanisms of stress-induced neuronal damage have not been precisely defined. We analyzed the molecular events related to apoptosis in the hippocampus of rats exposed to immobilization stress. Terminal dUTP nick end-labeling exhibited positive nuclei in the hippocampus of stressed rats, indicating DNA fragmentation. RT-PCR and Western blot analyses showed that immobilization stress increased and decreased the expression of pro-apoptotic gene bax and anti-apoptotic bcl-2 genes, respectively. Western blot analysis demonstrated that the characteristic 85 kDa apoptotic fragment of poly(ADP-ribose) polymerase (PARP) was not observed in the hippocampus subjected to immobilization stress. The amount of PARP protein was significantly reduced following stress. This study may provide a novel insight into molecular mechanisms implicated in hippocampal damage associated with stress.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / drug effects
  • Cell Death / physiology
  • Gene Expression Regulation, Enzymologic / physiology
  • Hippocampus / enzymology*
  • Hippocampus / pathology*
  • Hydrolysis
  • Male
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Stress, Physiological / enzymology*
  • Stress, Physiological / pathology*

Substances

  • Poly(ADP-ribose) Polymerase Inhibitors
  • Poly(ADP-ribose) Polymerases