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CNS Neurosci Ther. 2013 Aug;19(8):566-76. doi: 10.1111/cns.12114. Epub 2013 May 3.

The involvement of programmed cell death 5 (PDCD5) in the regulation of apoptosis in cerebral ischemia/reperfusion injury.

Author information

1
Department of Anatomy and Embryology, Peking University Health Science Center, Beijing, China.

Abstract

AIMS:

Programmed Cell Death 5 (PDCD5) is a protein that accelerates apoptosis in different types of cells in response to various stimuli and is down-regulated in many cancer tissues. We hypothesized in this study that down-regulating PDCD5 can protect the brain from ischemic damage by inhibiting PDCD5-induced apoptotic pathway.

METHODS:

One hundred and sixty male Sprague-Dawley rats were randomly assigned to five groups: Sham surgery (n = 25), MCAO (n = 45), MCAO+rhPDCD5 (RhPDCD5) (n = 30), MCAO+control siRNA (n = 30), and MCAO+PDCD5 siRNA (n = 30). At 24 h following MCAO, immunohistochemistry and Western blot were performed.

RESULTS:

PDCD5 siRNA reduced the infarct volume, improved neurological deficits, improved cerebral blood flow (CBF), and reduced Evans blue extravasation. Meanwhile, over-expression of PDCD5 protein with recombinant human PDCD5 (rhPDCD5) had an opposite effect. Immunohistochemistry and Western blot demonstrated PDCD5 siRNA decreased the expressions of key proapoptotic proteins such as p53, Bax/Bcl-2, and cleaved caspase-3 in the penumbra areas, whereas rhPDCD5 increased cell apoptosis. Double fluorescence labeling showed the positive immunoreactive materials of PDCD5 were partly colocalized with MAP2, GFAP, CD34, p53, and caspase-3 in the penumbra areas in brain.

CONCLUSIONS:

PDCD5-induced apoptosis and over-expression of PDCD5 are harmful to the ischemic neurons in vivo. Meanwhile, the inhibition of PDCD5 may be protective via reducing the apoptotic-related protein such as p53, Bax, and caspase-3. This observation may have potential for the treatment of ischemic cerebral stroke.

KEYWORDS:

Apoptosis; MCAO; PDCD5; siRNA in vivo

PMID:
23638963
DOI:
10.1111/cns.12114
[Indexed for MEDLINE]
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