Autophagic effect of programmed cell death 5 (PDCD5) after focal cerebral ischemic reperfusion injury in rats

Neurosci Lett. 2014 Apr 30;566:298-303. doi: 10.1016/j.neulet.2014.02.066. Epub 2014 Mar 12.

Abstract

Former studies indicated that programmed cell death 5 (PDCD5) protein could accelerate the process of apoptosis in response to some stimuli in various kinds of cells via the intrinsic or extrinsic pathway. In this study, we aimed to demonstrate for the first time that protein level of PDCD5 are related to autophagic activity after focal ischemic brain injury in rats. One hundred and twenty-five Sprague-Dawley rats (male) were randomly divided into the following groups: Sham operated, Middle Cerebral Artery Occlusion/Reperfusion (MCAO), MCAO+Control siRNA and MCAO+PDCD5 siRNA. Outcome measurements include neurobehavioral outcomes, brain infarct volume, brain water content, BBB disruption, MRI and double fluorescence labeling. Western blot and histopathophysiological techniques were used to measure the expression of PDCD5 and some pro-autophagic proteins such as Beclin 1 and the LC3-II/LC3-I ratio. The study found that decreased PDCD5 expression via intracerebroventricular injection of PDCD5 siRNA significantly improved the neurobehavioral outcome, reduced the infarct ratio, cerebral edema and BBB disruption. These results were associated with decreased expression of Beclin 1 and the LC3-II/LC3-I ratio in the penumbra area. Rapamycin, an inducer of autophagy, partially weakened the effect of PDCD5 siRNA. In conclusion, this study suggested that PDCD5 was a key regulator of autophagy that might play an important role following MCAO injury.

Keywords: Autophagy; MCAO; MRI; PDCD5; siRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins / genetics
  • Apoptosis Regulatory Proteins / metabolism*
  • Autophagy*
  • Beclin-1
  • Blood-Brain Barrier / metabolism
  • Brain Edema / metabolism
  • Brain Edema / pathology
  • Brain Infarction / metabolism
  • Brain Infarction / pathology
  • Infarction, Middle Cerebral Artery / complications
  • Ischemic Attack, Transient / etiology
  • Ischemic Attack, Transient / metabolism
  • Ischemic Attack, Transient / pathology*
  • Male
  • Microtubule-Associated Proteins / metabolism
  • RNA, Small Interfering / genetics
  • Rats, Sprague-Dawley
  • Reperfusion Injury / etiology
  • Reperfusion Injury / metabolism
  • Reperfusion Injury / pathology*
  • Sirolimus / pharmacology

Substances

  • Apoptosis Regulatory Proteins
  • Beclin-1
  • Becn1 protein, rat
  • LC3 protein, rat
  • Microtubule-Associated Proteins
  • PDCD5 protein, rat
  • RNA, Small Interfering
  • Sirolimus