C/EBP homologous protein (CHOP) mediates neuronal apoptosis in rats with spinal cord injury

Wang,Zhangfu; Zhang,Chuanyi; Hong,Zhenghua; Chen,Haixiao; Chen,Weifu; Chen,Guofu

doi:10.3892/etm.2012.745

C/EBP homologous protein (CHOP) mediates neuronal apoptosis in rats with spinal cord injury

Authors:
- Zhangfu Wang
- Chuanyi Zhang
- Zhenghua Hong
- Haixiao Chen
- Weifu Chen
- Guofu Chen
View Affiliations

Affiliations: Department of Orthopedics, Taizhou Hospital of Zhejiang Province, Taizhou, Zhejiang 317000, P.R. China
Published online on: October 12, 2012 https://doi.org/10.3892/etm.2012.745
Pages: 107-111

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Spinal cord injury (SCI) is a severe health problem and the mechanism involved remains elusive. The aim of the present study was to elucidate the role of C/EBP homologous protein (CHOP), a prominent protein of the endoplasmic reticulum (ER) stress-mediated apoptosis in SCI. A total of 20 adult male Sprague-Dawley rats were divided into two groups at random, ten rats were subjected to a modified Allen's test (using a weight-drop device) to induce a SCI model and the remaining ten rats only had the corresponding vertebral lamina removed with no injury and served as the sham-operated group. Pathological changes in the spinal cord were observed 12 h after injury by hematoxylin and eosin staining and TUNEL staining was performed to visualize apoptotic cells. The expression of CHOP was also detected by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction. The results showed that a typical apoptotic morphology, namely the increased the number of TUNEL-positive cells in the injured spinal cord. The expression levels of CHOP in the rats with SCI were increased compared with the sham-operated rats (P<0.05). These results revealed that CHOP-mediated ER stress-induced apoptosis may be involved in SCI.

View Figures

View References

1	Lidal IB, Veenstra M, Hjeltnes N and Biering-Sørensen F: Health-related quality of life in persons with long-standing spinal cord injury. Spinal Cord. 46:710–715. 2008. View Article : Google Scholar : PubMed/NCBI
2	Müller R, Peter C, Cieza A and Geyh S: The role of social support and social skills in people with spinal cord injury - a systematic review of the literature. Spinal Cord. 50:94–106. 2012.PubMed/NCBI
3	Zou W, Guo Q, Chen C, Yang Y and Wang E: Intrathecal herpes simplex virus type 1 amplicon vector-mediated human proenkephalin reduces chronic constriction injury-induced neuropathic pain in rats. Mol Med Report. 4:529–533. 2011.
4	Liu WM, Wu JY, Li FC and Chen QX: Ion channel blockers and spinal cord injury. J Neurosci Res. 89:791–801. 2011. View Article : Google Scholar : PubMed/NCBI
5	Dumont RJ, Okonkwo DO, Verma S, et al: Acute spinal cord injury, part I: pathophysiologic mechanisms. Clin Neuropharmacol. 24:254–264. 2001. View Article : Google Scholar : PubMed/NCBI
6	Park E, Velumian AA and Fehlings MG: The role of excitotoxicity in secondary mechanisms of spinal cord injury: a review with an emphasis on the implications for white matter degeneration. J Neurotrauma. 21:754–774. 2004. View Article : Google Scholar : PubMed/NCBI
7	Liu XZ, Xu XM, Hu R, et al: Neuronal and glial apoptosis after traumatic spinal cord injury. J Neurosci. 17:5395–5406. 1997.PubMed/NCBI
8	Martin LJ: Neuronal cell death in nervous system development, disease, and injury (Review). Int J Mol Med. 7:455–478. 2001.PubMed/NCBI
9	Brostrom MA and Brostrom CO: Calcium dynamics and endoplasmic reticular function in the regulation of protein synthesis: implications for cell growth and adaptability. Cell Calcium. 34:345–363. 2003. View Article : Google Scholar : PubMed/NCBI
10	de Almeida SF, Fleming JV, Azevedo JE, Carmo-Fonseca M and de Sousa M: Stimulation of an unfolded protein response impairs MHC class I expression. J Immunol. 178:3612–3619. 2007.PubMed/NCBI
11	Foufelle F and Ferré P: Unfolded protein response: its role in physiology and physiopathology. Med Sci (Paris). 23:291–296. 2007.(In French).
12	Kaneko M and Nomura Y: ER signaling in unfolded protein response. Life Sci. 74:199–205. 2003. View Article : Google Scholar : PubMed/NCBI
13	Wang F, Song W, Brancati G and Segatori L: Inhibition of endoplasmic reticulum-associated degradation rescues native folding in loss of function protein misfolding diseases. J Biol Chem. 286:43454–43464. 2011. View Article : Google Scholar : PubMed/NCBI
14	Cox DJ, Strudwick N, Ali AA, Paton AW, Paton JC and Schröder M: Measuring signaling by the unfolded protein response. Methods Enzymol. 491:261–292. 2011. View Article : Google Scholar : PubMed/NCBI
15	Oyadomari S and Mori M: Roles of CHOP/GADD153 in endoplasmic reticulum stress. Cell Death Differ. 11:381–389. 2004. View Article : Google Scholar : PubMed/NCBI
16	Oida Y, Shimazawa M, Imaizumi K and Hara H: Involvement of endoplasmic reticulum stress in the neuronal death induced by transient forebrain ischemia in gerbil. Neuroscience. 151:111–119. 2008. View Article : Google Scholar : PubMed/NCBI
17	Silva RM, Ries V, Oo TF, et al: CHOP/GADD153 is a mediator of apoptotic death in substantia nigra dopamine neurons in an in vivo neurotoxin model of parkinsonism. J Neurochem. 95:974–986. 2005. View Article : Google Scholar : PubMed/NCBI
18	Basso DM, Beattie MS, Bresnahan JC, et al: MASCIS evaluation of open field locomotor scores: effects of experience and teamwork on reliability. Multicenter Animal Spinal Cord Injury Study. J Neurotrauma. 7:343–359. 1996. View Article : Google Scholar : PubMed/NCBI
19	Dang AB, Tay BK, Kim HT, Nauth A, Alfonso-Jaume MA and Lovett DH: Inhibition of MMP2/MMP9 after spinal cord trauma reduces apoptosis. Spine (Phila Pa 1976). 33:E576–E579. 2008. View Article : Google Scholar : PubMed/NCBI
20	Chen KB, Uchida K, Nakajima H, et al: Tumor necrosis factor-alpha antagonist reduces apoptosis of neurons and oligodendroglia in rat spinal cord injury. Spine (Phila Pa 1976). 36:1350–1358. 2011. View Article : Google Scholar : PubMed/NCBI
21	Yuan J and Yankner BA: Apoptosis in the nervous system. Nature. 407:802–809. 2000. View Article : Google Scholar
22	Eldadah BA and Faden AI: Caspase pathways, neuronal apoptosis, and CNS injury. J Neurotrauma. 17:811–829. 2000. View Article : Google Scholar : PubMed/NCBI
23	Ferri KF and Kroemer G: Organelle-specific initiation of cell death pathways. Nat Cell Biol. 3:E255–E263. 2001. View Article : Google Scholar : PubMed/NCBI
24	Lehotský J, Kaplán P, Babusíková E, Strapková A and Murín R: Molecular pathways of endoplasmic reticulum dysfunctions: possible cause of cell death in the nervous system. Physiol Res. 52:269–274. 2003.PubMed/NCBI
25	Sakurai M, Takahashi G, Abe K, Horinouchi T, Itoyama Y and Tabayashi K: Endoplasmic reticulum stress induced in motor neurons by transient spinal cord ischemia in rabbits. J Thorac Cardiovasc Surg. 130:640–645. 2005. View Article : Google Scholar : PubMed/NCBI
26	Ogawa S, Kitao Y and Hori O: Ischemia-induced neuronal cell death and stress response. Antioxid Redox Signal. 9:573–587. 2007. View Article : Google Scholar : PubMed/NCBI
27	Nagata T, Ilieva H, Murakami T, et al: Increased ER stress during motor neuron degeneration in a transgenic mouse model of amyotrophic lateral sclerosis. Neurol Res. 29:767–771. 2007. View Article : Google Scholar : PubMed/NCBI
28	DeGracia DJ and Montie HL: Cerebral ischemia and the unfolded protein response. J Neurochem. 91:1–8. 2004. View Article : Google Scholar : PubMed/NCBI
29	Chiribau CB, Gaccioli F, Huang CC, Yuan CL and Hatzoglou M: Molecular symbiosis of CHOP and C/EBP beta isoform LIP contributes to endoplasmic reticulum stress-induced apoptosis. Mol Cell Biol. 30:3722–3731. 2010. View Article : Google Scholar : PubMed/NCBI
30	Ling ZQ, Tian Q, Wang L, et al: Constant illumination induces Alzheimer-like damages with endoplasmic reticulum involvement and the protection of melatonin. J Alzheimers Dis. 16:287–300. 2009.PubMed/NCBI