Brain trauma induces X‐box protein 1 processing indicative of activation of the endoplasmic reticulum unfolded protein response

作者: Wulf Paschen , Ido Yatsiv , Shai Shoham , Esther Shohami

DOI: 10.1046/J.1471-4159.2003.02218.X

关键词:

摘要: Brain trauma was induced in mice using a closed head injury (CHI) model. At 1, 6 or 24 h after trauma, brains were dissected into the cortex, striatum and hippocampus. Changes levels of processed X-box protein 1 (xbp1), glucose-regulated 78 (grp78), growth arrest DNA damage-inducible gene 153 (gadd153) heat-shock 70 (hsp70) mRNA, indicating impaired endoplasmic reticulum (ER) cytoplasmic functioning, evaluated by quantitative PCR. In xbp1 mRNA rose to 2000% control CHI, stayed high throughout experiments. hippocampus striatum, delayed fashion, peaking at (1000% control) CHI (1500% respectively. Levels grp78 only slightly increased cortex (150% control), unchanged transiently decreased striatum. gadd153 did not change significantly trauma. A transient rise hsp70 observed (600% control). Processing is sign activation unfolded response indicative ER dysfunction. The results suggest that brain induces dysfunction, which spreads from ipsilateral These observations may have clinical implications should therefore be considered for future investigations on therapeutic intervention caused contusion-induced neurotrauma.

参考文章(58)
T Liu, G Z Feuerstein, F C Barone, Cytokines, inflammation, and brain injury: role of tumor necrosis factor-alpha. Cerebrovascular and brain metabolism reviews. ,vol. 6, pp. 341- 360 ,(1994)
Theodor Petrov, Bill D. Underwood, Benjamin Braun, Sarah S. Alousi, José A. Rafols, Upregulation of iNOS Expression and Phosphorylation of eIF-2α Are Paralleled by Suppression of Protein Synthesis in Rat Hypothalamus in a Closed Head Trauma Model Journal of Neurotrauma. ,vol. 18, pp. 799- 812 ,(2001) , 10.1089/089771501316919166
G Kuznetsov, M.A. Brostrom, C.O. Brostrom, Demonstration of a calcium requirement for secretory protein processing and export. Differential effects of calcium and dithiothreitol. Journal of Biological Chemistry. ,vol. 267, pp. 3932- 3939 ,(1992) , 10.1016/S0021-9258(19)50615-9
H.F. Lodish, N Kong, L Wikström, Calcium is required for folding of newly made subunits of the asialoglycoprotein receptor within the endoplasmic reticulum. Journal of Biological Chemistry. ,vol. 267, pp. 12753- 12760 ,(1992) , 10.1016/S0021-9258(18)42340-X
T.K. Ghosh, J.H. Bian, A.D. Short, S.L. Rybak, D.L. Gill, Persistent intracellular calcium pool depletion by thapsigargin and its influence on cell growth. Journal of Biological Chemistry. ,vol. 266, pp. 24690- 24697 ,(1991) , 10.1016/S0021-9258(18)54285-X
YUN CHEN, SHLOMO CONSTANTINI, VICTORIA TREMBOVLER, MARTA WEINSTOCK, ESTHER SHOHAMI, An experimental model of closed head injury in mice: pathophysiology, histopathology, and cognitive deficits. Journal of Neurotrauma. ,vol. 13, pp. 557- 568 ,(1996) , 10.1089/NEU.1996.13.557
H F Lodish, N Kong, Perturbation of cellular calcium blocks exit of secretory proteins from the rough endoplasmic reticulum. Journal of Biological Chemistry. ,vol. 265, pp. 10893- 10899 ,(1990) , 10.1016/S0021-9258(19)38530-8
Esther Shohami, Illana Gozes, Douglas E. Brenneman, Ruth A. Steingart, Yaniv Assaf, Yoram Cohen, Oded Eizenberg, Victoria Trembolver, Liana Beni-Adani, A Peptide Derived from Activity-Dependent Neuroprotective Protein (ADNP) Ameliorates Injury Response in Closed Head Injury in Mice Journal of Pharmacology and Experimental Therapeutics. ,vol. 296, pp. 57- 63 ,(2001)
Rita Kumar, Salman Azam, Jonathan M. Sullivan, Cheri Owen, Douglas R. Cavener, Peichuan Zhang, David Ron, Heather P. Harding, Jane-Jane Chen, Anping Han, Blaine C. White, Gary S. Krause, Donald J. DeGracia, Brain ischemia and reperfusion activates the eukaryotic initiation factor 2α kinase, PERK Journal of Neurochemistry. ,vol. 77, pp. 1418- 1421 ,(2001) , 10.1046/J.1471-4159.2001.00387.X