Open AccessThe Involvement of Programmed Cell Death 5 ( PDCD 5) in the Regulation of Apoptosis in Cerebral Ischemia/Reperfusion Injury
Author(s) -
Chen ChunHua,
Jiang Zhao,
Yan JunHao,
Yang Lei,
Wang Ke,
Chen YingYu,
Han JingYan,
Zhang John H.,
Zhou ChangMan
Publication year - 2013
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.12114
Subject(s) - penumbra , apoptosis , western blot , programmed cell death , blot , ischemia , immunohistochemistry , flow cytometry , medicine , cell , chemistry , cancer research , microbiology and biotechnology , pathology , biology , immunology , biochemistry , gene
Summary Aims Programmed Cell Death 5 ( PDCD 5) 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 PDCD 5 can protect the brain from ischemic damage by inhibiting PDCD 5‐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 +rh PDCD 5 (Rh PDCD 5) (n = 30), MCAO +control si RNA (n = 30), and MCAO + PDCD 5 si RNA (n = 30). At 24 h following MCAO , immunohistochemistry and Western blot were performed. Results PDCD 5 si RNA reduced the infarct volume, improved neurological deficits, improved cerebral blood flow ( CBF ), and reduced Evans blue extravasation. Meanwhile, over‐expression of PDCD 5 protein with recombinant human PDCD 5 (rh PDCD 5) had an opposite effect. Immunohistochemistry and Western blot demonstrated PDCD 5 si RNA decreased the expressions of key proapoptotic proteins such as p53, Bax/Bcl‐2, and cleaved caspase‐3 in the penumbra areas, whereas rh PDCD 5 increased cell apoptosis. Double fluorescence labeling showed the positive immunoreactive materials of PDCD 5 were partly colocalized with MAP 2, GFAP , CD 34, p53, and caspase‐3 in the penumbra areas in brain. Conclusions PDCD 5‐induced apoptosis and over‐expression of PDCD 5 are harmful to the ischemic neurons in vivo . Meanwhile, the inhibition of PDCD 5 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.