title: Over-expression of PUMA correlates with the apoptosis of spinal cord cells in rat neuropathic intermittent claudication model.
abstract: BACKGROUND
  Neuropathic intermittent claudication (NIC) is a typical clinical symptom of lumbar spinal stenosis and the apoptosis of neurons caused by cauda equina compression (CEC) has been proposed as an important reason. Whereas, the factors and the mechanism involved in the process of apoptosis induced by CEC remain unclear.
  
  
  RESULTS
  In our modified rat model of NIC, a trapezoid-shaped silicon rubber was inserted into the epidural space under the L5 and L6 vertebral plate. Obvious apoptosis was observed in spinal cord cells after compression by TUNEL assay. Simultaneously, qRT-PCR and immunohistochemistry showed that the expression levels of PUMA (p53 up-regulated modulator of apoptosis) and p53 were upregulated significantly in spinal cord under compression, while the expression of p53 inhibitor MDM2 and SirT2 decreased in the same region. Furthermore, CEC also resulted in the upregulation of Bcl-2 pro-apoptotic genes expression and caspase-3 activation. With the protection of Methylprednisolone, the upregulation of PUMA and p53 expression as well as the decrease of MDM2 and SirT2 in spinal cord were partially rescued in western bolt analysis.
  
  
  CONCLUSIONS
  These results suggest that over-expression of PUMA correlates with CEC caused apoptosis of spinal cord cells, which is characterized by the increase of p53, Bax and Bad expression. PUMA upregulation might be crucial to induce apoptosis of spinal cord cells through p53-dependent pathway in CEC.
authors: Department of Spine Surgery, Bone and Joint Medical Center, East Hospital, Tongji University School of Medicine, Shanghai, China.
authors: Bin
authors: B
authors: Ma
authors: Jiangang
authors: J
authors: Shi
authors: Lianshun
authors: L
authors: Jia
authors: Wen
authors: W
authors: Yuan
authors: Jianfeng
authors: J
authors: Wu
authors: Zhiyi
authors: Z
authors: Fu
authors: Yuan
authors: Y
authors: Wang
authors: Ning
authors: N
authors: Liu
authors: Zhengmao
authors: Z
authors: Guan
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001522:Behavior, Animal; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D007383:Intermittent Claudication / Q000235:genetics* / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D056565:Sirtuin 2 / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D013127:Spinal Nerves / Q000473:pathology / Q000503:physiopathology; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D051017:Apoptosis Regulatory Proteins; C533952:Bbc3 protein, rat; C097475:Sirt2 protein, rat; D016159:Tumor Suppressor Protein p53; D056565:Sirtuin 2
references: Spine (Phila Pa 1976). 1992 Jan;17(1):9-15
references: 1536018
references: J Neurosci Methods. 2001 Jan 15;104(2):191-8
references: 11164245
references: Br Med J. 1964 Oct 17;2(5415):985-7
references: 14185688
references: Spine (Phila Pa 1976). 2007 Mar 15;32(6):627-34
references: 17413466
references: Neuroscience. 1997 Apr;77(4):1115-22
references: 9130791
references: J Orthop Res. 1989;7(6):817-23
references: 2795321
references: J Neuropathol Exp Neurol. 2009 Jul;68(7):747-56
references: 19535997
references: J Spinal Disord. 1997 Dec;10(6):499-504
references: 9438815
references: J Neurotrauma. 1995 Feb;12(1):1-21
references: 7783230
references: J Neurosci. 1999 Sep 15;19(18):7860-9
references: 10479688
references: Spine (Phila Pa 1976). 1998 Aug 1;23(15):1641-4
references: 9704369
references: J Cell Biol. 2009 Apr 20;185(2):279-90
references: 19380879
references: J Spinal Disord Tech. 2009 Apr;22(2):130-4
references: 19342935
references: Spine (Phila Pa 1976). 1999 May 1;24(9):845-51
references: 10327504
references: Exp Neurol. 1985 Aug;89(2):408-19
references: 4018210
references: J Neurosci. 2007 Nov 21;27(47):12989-99
references: 18032672
references: Biochem Biophys Res Commun. 2008 Apr 11;368(3):690-5
references: 18249187
references: Biochem Biophys Res Commun. 2005 Jun 10;331(3):761-77
references: 15865932
references: Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):7834-8
references: 7644501
references: J Neurosci. 2010 Dec 15;30(50):16938-48
references: 21159964
references: Spine (Phila Pa 1976). 2004 May 15;29(10):1105-11
references: 15131438
references: J Neurosci. 2004 Nov 3;24(44):10003-12
references: 15525786
references: Neuroreport. 2002 Jan 21;13(1):101-6
references: 11924868