Abstract
BAG-1 protein was initially identified as a Bcl-2-binding protein. It was reported to enhance Bcl-2 protection from cell death, suggesting that BAG-1 represents a new type of anti-cell death gene. Moreover, recent study has shown that BAG-1 can enhance the proliferation of neuronal precursor cells, attenuate the growth inhibition induced by siah1. However, its function and expression in the central nervous system lesion are not been understood very well. In this study, we performed a traumatic brain injury (TBI) model in adult rats and investigated the dynamic changes of BAG-1 expression in the brain cortex. Double immunofluorescence staining revealed that BAG-1 was co-expressed with NEURON and glial fibrillary acidic protein (GFAP). In addition, we detected that proliferating cell nuclear antigen had the co-localization with GFAP, and BAG-1. All our findings suggested that BAG-1 might involve in the pathophysiology of brain after TBI.
Similar content being viewed by others
Abbreviations
- BAG-1:
-
Bcl-2-associated athanogene-1
- CNS:
-
Central nervous system
- PAGE:
-
Polyacrylamide gel electrophoresis
- ECL:
-
Enhanced chemiluminescence system
- BSA:
-
Bovine serum albumin
- NeuN:
-
Neuronal nuclei
- GFAP:
-
Glial fibrillary acidic protein
- CASPASE-3:
-
Cysteinyl aspartate-specific protease 3
- PCNA:
-
Proliferating cell nuclear antigen
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
References
Adachi M, Sekiya M, Torigoe T, Takayama S, Reed JC, Miyazaki T, Minami Y, Taniguchi T, Imai K (1996) Interleukin-2 (IL-2) upregulates BAG-1 gene expression through serine-rich region within IL-2 receptor beta c chain. Blood 88:4118–4123
Anderson LR, Sutherland RL, Butt AJ (2010) BAG-1 overexpression attenuates luminal apoptosis in MCF-10A mammary epithelial cells through enhanced RAF-1 activation. Oncogene 29(4):527–538
Bye N, Carron S, Han X, Agyapomaa D, Ng SY, Yan E, Rosenfeld JV, Morganti-Kossmann MC (2011) Neurogenesis and glial proliferation are stimulated following diffuse traumatic brain injury in adult rats. J Neurosci Res 89:986–1000
Campbell JN, Churn SB, Register D (2012) Traumatic brain injury causes an FK506-sensitive loss and an overgrowth of dendritic spines in rat forebrain. J Neurotrauma 29(2):201–217
Chen M, Clark RS, Kochanek PM, Chen J, Schiding JK, Stetler RA, Graham SH (1998) 72-kDa heat shock protein and mRNA expression after controlled cortical impact injury with hypoxemia in rats. J Neurotrauma 15:171–181
Clark RS, Chen J, Watkins SC, Kochanek PM, Chen M, Stetler RA, Loeffert JE, Graham SH (1997) Apoptosis-suppressor gene bcl-2 expression after traumatic brain injury in rats. J Neurosci 17:9172–9182
Clevenger CV, Thickman K, Ngo W, Chang WP, Takayama S, Reed JC (1997) Role of Bag-1 in the survival and proliferation of the cytokine-dependent lymphocyte lines Ba/F3 and Nb2. Mol Endocrinol 11:608–618
Crochemore C, Michaelidis TM, Fischer D, Loeffler JP, Almeida OF (2002) Enhancement of p53 activity and inhibition of neural cell proliferation by glucocorticoid receptor activation. FASEB J 16:761–770
Crocoll A, Blum M, Cato AC (2000) Isoform-specific expression of BAG-1 in mouse development. Mech Dev 91:355–359
Crossin KL, Tai MH, Krushel LA, Mauro VP, Edelman GM (1997) Glucocorticoid receptor pathways are involved in the inhibition of astrocyte proliferation. Proc Natl Acad Sci USA 94:2687–2692
Di Giovanni S, Movsesyan V, Ahmed F, Cernak I, Schinelli S, Stoica B, Faden AI (2005) Cell cycle inhibition provides neuroprotection and reduces glial proliferation and scar formation after traumatic brain injury. Proc Natl Acad Sci USA 102:8333–8338
Elliott E, Ginzburg I (2009) BAG-1 is preferentially expressed in neuronal precursor cells of the adult mouse brain and regulates their proliferation in vitro. FEBS Lett 583:229–234
Feeney DM, Boyeson MG, Linn RT, Murray HM, Dail WG (1981) Responses to cortical injury: I methodology and local effects of contusions in the rat. Brain Res 211:67–77
Hayashi T, Sakai K, Sasaki C, Itoyama Y, Abe K (2000) Loss of bag-1 immunoreactivity in rat brain after transient middle cerebral artery occlusion. Brain Res 85:496–500
Keane RW, Kraydieh S, Lotocki G, Alonso OF, Aldana P, Dietrich WD (2001) Apoptotic and antiapoptotic mechanisms after traumatic brain injury. J Cereb Blood Flow Metab 21:1189–1198
Langlois JA, Rutland-Brown W, Wald MM (2006) The epidemiology and impact of traumatic brain injury: a brief overview. J Head Trauma Rehabil 21:375–378
Lee MY, Ju WK, Cha JH, Son BC, Chun MH, Kang JK, Park CK (1999) Expression of vascular endothelial growth factor mRNA following transient forebrain ischemia in rats. Neurosci Lett 265:107–110
Liman J, Ganesan S, Dohm CP, Krajewski S, Reed JC, Bahr M, Wouters FS, Kermer P (2005) Interaction of BAG1 and Hsp70 mediates neuroprotectivity and increases chaperone activity. Mol Cell Biol 25:3715–3725
Lu J (2009) The anti-proliferation mechanism of glucocorticoid mediated by glucocorticoid receptor-regulating gene expression. Pathophysiol 16:267–272
Marshall LF (2000) Epidemiology and cost of central nervous system injury. Clin Neurosurg 46:105–112
Matsuzawa S, Takayama S, Froesch BA, Zapata JM, Reed JC (1998) p53-inducible human homologue of Drosophila seven in absentia (Siah) inhibits cell growth: suppression by BAG-1. EMBO J 17:2736–2747
Packham G (1997) Mammalian cells express two differently localized Bag-1 isoforms generated by alternative translation initiation. Biochem J 328:807–813
Planchamp V, Bermel C, Tonges L, Ostendorf T (2008) BAG1 promotes axonal outgrowth and regeneration in vivo via Raf-1 and reduction of ROCK activity. Brain 131:2606–2619
Raghupathi R, Graham DI, McIntosh TK (2000) Apoptosis after traumatic brain injury. J Neurotrauma 17:927–938
Ridet JL, Malhotra SK, Privat A, Gage FH (1997) Reactive astrocytes: cellular and molecular cues to biological function. Trends Neurosci 20:570–577
Schneikert J, Hubner S, Martin E, Cato AC (1999) A nuclear action of the eukaryotic cochaperone RAP46 in downregulation of glucocorticoid receptor activity. J Cell Biol 146:929–940
Schulz JB, Bremen D, Reed JC, Lommatzsch J, Takayama S, Wullner U, Loschmann PA, Klockgether T, Weller M (1997) Cooperative interception of neuronal apoptosis by BCL-2 and BAG-1 expression: prevention of caspase activation and reduced production of reactive oxygen species. J Neurochem 69:2075–2086
Sourisseau T, Desbois C, Debure L, Bowtell DD, Cato AC, Schneikert J, Moyse E, Michel D (2001) Alteration of the stability of Bag-1 protein in the control of olfactory neuronal apoptosis. J Cell Sci 114:1409–1416
Southern SL, Collard TJ, Urban BC, Skeen VR, Smartt HJ, Hague A, Oakley F, Townsend PA, Perkins ND, Paraskeva C, Williams AC (2011) BAG-1 interacts with the p50-p50 homodimeric NF-kappaB complex: implications for colorectal carcinogenesis. Oncogene. doi:10.1038/onc.2011.452
Swanson RA (1992) Astrocyte glutamate uptake during chemical hypoxia in vitro. Neurosci Lett 147:143–146
Takayama S, Reed JC (2001) Molecular chaperone targeting and regulation by BAG family proteins. Nat Cell Biol 3:237–241
Takayama S, Sato T, Krajewski S, Kochel K, Irie S, Millan JA, Reed JC (1995) Cloning and functional analysis of BAG-1: a novel Bcl-2-binding protein with anti-cell death activity. Cell 80:279–284
Takayama S, Bimston DN, Matsuzawa S, Freeman BC, Aime-Sempe C, Xie Z, Morimoto RI, Reed JC (1997) BAG-1 modulates the chaperone activity of Hsp70/Hsc70. EMBO J 16:4887–4896
Takayama S, Krajewski S, Krajewska M, Kitada S, Zapata JM, Kochel K, Knee D, Scudiero D, Tudor G, Miller GJ, Miyashita T, Yamada M, Reed JC (1998) Expression and location of Hsp70/Hsc-binding anti-apoptotic protein BAG-1 and its variants in normal tissues and tumor cell lines. Cancer Res 58:3116–3131
Wang HG, Takayama S, Rapp UR, Reed JC (1996) Bcl-2 interacting protein, BAG-1, binds to and activates the kinase Raf-1. Proc Natl Acad Sci 93(14):7063–7068
Zeiner M, Gebauer M, Gehring U (1997) Mammalian protein RAP46: an interaction partner and modulator of 70 kDa heat shock proteins. EMBO J 16:5483–5490
Acknowledgments
This work was supported by the National Natural Science Foundation of China (No. 31071228 and No. 30670648); Nature Science Foundation of Jiangsu Colleges and Universities Grant (09KJB320011); A Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
Author information
Authors and Affiliations
Corresponding authors
Rights and permissions
About this article
Cite this article
Xu, T., Wang, X., Cao, M. et al. Increased expression of BAG-1 in rat brain cortex after traumatic brain injury. J Mol Hist 43, 335–342 (2012). https://doi.org/10.1007/s10735-012-9408-0
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10735-012-9408-0