title: The involvement of programmed cell death 5 (PDCD5) in the regulation of apoptosis in cerebral ischemia/reperfusion injury.
abstract: OBJECTIVE
  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.
authors: Department of Anatomy and Embryology, Peking University Health Science Center, Beijing, China.
authors: Chun-Hua
authors: CH
authors: Chen
authors: Zhao
authors: Z
authors: Jiang
authors: Jun-Hao
authors: JH
authors: Yan
authors: Lei
authors: L
authors: Yang
authors: Ke
authors: K
authors: Wang
authors: Ying-Yu
authors: YY
authors: Chen
authors: Jing-Yan
authors: JY
authors: Han
authors: John H
authors: JH
authors: Zhang
authors: Chang-Man
authors: CM
authors: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000502:physiology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology* / Q000517:prevention & control
chemical_list: D051017:Apoptosis Regulatory Proteins; D009363:Neoplasm Proteins; C117283:PDCD5 protein, human
keywords: Apoptosis; MCAO; PDCD5; siRNA in vivo
references: Leuk Res. 2006 Sep;30(9):1159-65
references: 16507320
references: Biophys J. 2011 Dec 7;101(11):2582-91
references: 22261045
references: Nature. 1998 Jan 29;391(6666):496-9
references: 9461218
references: Exp Neurol. 2005 Jan;191(1):198-210
references: 15589527
references: Brain Res. 2011 Jan 7;1367:347-59
references: 20950592
references: Brain Res. 2002 Feb 1;926(1-2):165-71
references: 11814419
references: Oncol Rep. 2012 Jul;28(1):91-8
references: 22484667
references: Apoptosis. 2006 Jan;11(1):101-11
references: 16374546
references: Apoptosis. 2010 Jul;15(7):805-13
references: 20349137
references: Biochem Biophys Res Commun. 1999 Jan 8;254(1):203-10
references: 9920759
references: Proc Natl Acad Sci U S A. 2001 Dec 18;98(26):15089-94
references: 11752456
references: N Engl J Med. 2001 Feb 22;344(8):539-48
references: 11207349
references: Oncol Rep. 2008 Sep;20(3):573-9
references: 18695908
references: Neoplasia. 2009 Apr;11(4):345-54
references: 19308289
references: Exp Neurol. 2009 Mar;216(1):35-46
references: 19073180
references: J Pharmacol Exp Ther. 2005 Mar;312(3):1249-56
references: 15528451
references: Stroke. 1989 Jan;20(1):84-91
references: 2643202
references: Toxicol Pathol. 2007 Jun;35(4):495-516
references: 17562483
references: Stroke. 1995 Apr;26(4):627-34; discussion 635
references: 7709410
references: FEBS Lett. 2001 Dec 7;509(2):191-6
references: 11741587
references: J Cereb Blood Flow Metab. 2003 Jul;23(7):855-64
references: 12843789
references: Chest. 2012 Feb;141(2 Suppl):e601S-e636S
references: 22315273
references: J Cell Sci. 2004 Mar 15;117(Pt 8):1525-32
references: 15020679
references: Stroke. 2000 Aug;31(8):1974-80; discussion 1981
references: 10926966
references: Exp Neurol. 2012 Mar;234(1):181-90
references: 22227058
references: Acta Neurochir Suppl. 2002;81:253-6
references: 12168319
references: Life Sci. 2002 Aug 30;71(15):1771-8
references: 12151055
references: J Biol Chem. 2006 Aug 25;281(34):24803-17
references: 16754680
references: Eur J Pharmacol. 2010 Dec 15;649(1-3):120-6
references: 20869960
references: J Cereb Blood Flow Metab. 2005 May;25(5):554-71
references: 15703702
references: Apoptosis. 2006 Jun;11(6):993-1001
references: 16547588
references: Exp Neurol. 2012 Oct;237(2):453-63
references: 22868201
references: Cell Biochem Biophys. 2005;43(3):355-63
references: 16247177
references: Neurobiol Dis. 2009 Mar;33(3):509-17
references: 19166937
references: Acta Neurochir (Wien). 1991;109(3-4):126-32
references: 1858530