Skip to main content
Log in

The Expression Changes of Cystathionine-β-synthase in Brain Cortex After Traumatic Brain Injury

  • Published:
Journal of Molecular Neuroscience Aims and scope Submit manuscript

Abstract

Cystathionine-β-synthase (CBS) catalyzes the condensation of serine with homocysteine to form cystathionine and occupies a crucial regulatory position between the methionine cycle and the biosynthesis of cysteine by transsulfuration. It was reported that CBS was a novel marker of both differentiation and proliferation for certain cell types, suggesting that CBS represents a survival-promoting protein. However, its expression and function in the central nervous system lesion are not well understood. To investigate changes of CBS after traumatic brain injury (TBI) and its possible role, mice TBI model was established by controlled cortical impact system, and the expression and cellular localization of CBS after TBI was investigated in the present study. Western blot analysis revealed that CBS was present in normal mice brain cortex. It gradually decreased, reached a valley at the third day after TBI, and then restored to basal level. Importantly, more CBS was colocalized with neuron. In addition, Western blot detection showed that the third day postinjury was also the apoptosis peak indicated by the elevated expression of caspase-3. Importantly, immunohistochemistry analysis revealed that injury-induced expression of CBS was colabeled by Bcl-2 and had no co-localization with caspase-3. These data suggested that CBS may be implicated in the apoptosis of neuron and involved in the pathophysiology of brain after TBI.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  • Abe K, Kimura H (1996) The possible role of hydrogen sulfide as an endogenous neuromodulator. J Neurosci 16:1066–1071

    PubMed  CAS  Google Scholar 

  • Abekhoukh S, Planque C, Ripoll C, Urbaniak P, Paul JL, Delabar JM, Janel N (2012) Dyrk1A, a serine/threonine kinase, is involved in ERK and Akt activation in the brain of hyperhomocysteinemic mice. Mol Neurobiol. doi:10.1007/s12035-12012-18326-12031

  • Bao L, Vlcek C, Paces V, Kraus JP (1998) Identification and tissue distribution of human cystathionine beta-synthase mRNA isoforms. Arch Biochem Biophys 350:95–103

    Article  PubMed  CAS  Google Scholar 

  • Bateman A (1997) The structure of a domain common to archaebacteria and the homocystinuria disease protein. Trends Biochem Sci 22:12–13

    Article  PubMed  CAS  Google Scholar 

  • Bermpohl D, You Z, Korsmeyer SJ, Moskowitz MA, Whalen MJ (2006) Traumatic brain injury in mice deficient in Bid: effects on histopathology and functional outcome. J Cereb Blood Flow Metab 26:625–633

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Wu X, Shao B, Zhao W, Shi W, Zhang S, Ni L, Shen A (2011) Increased expression of TNF receptor-associated factor 6 after rat traumatic brain injury. Cell Mol Neurobiol 31:269–275

    Article  PubMed  Google Scholar 

  • Dutta S, Sinha S, Chattopadhyay A, Gangopadhyay PK, Mukhopadhyay J, Singh M, Mukhopadhyay K (2005) Cystathionine beta-synthase T833C/844INS68 polymorphism: a family-based study on mentally retarded children. Behav Brain Funct 1:25

    Article  PubMed  Google Scholar 

  • Enokido Y, Suzuki E, Iwasawa K, Namekata K, Okazawa H, Kimura H (2005) Cystathionine beta-synthase, a key enzyme for homocysteine metabolism, is preferentially expressed in the radial glia/astrocyte lineage of developing mouse CNS. FASEB J 19:1854–1856

    PubMed  CAS  Google Scholar 

  • Ganapathy PS, Moister B, Roon P, Mysona BA, Duplantier J, Dun Y, Moister TK, Farley MJ, Prasad PD, Liu K, Smith SB (2009) Endogenous elevation of homocysteine induces retinal neuron death in the cystathionine-beta-synthase mutant mouse. Invest Ophthalmol Vis Sci 50:4460–4470

    Article  PubMed  Google Scholar 

  • Geng B, Chang L, Pan C, Qi Y, Zhao J, Pang Y, Du J, Tang C (2004) Endogenous hydrogen sulfide regulation of myocardial injury induced by isoproterenol. Biochem Biophys Res Commun 318:756–763

    Article  PubMed  CAS  Google Scholar 

  • Han Y, Qin J, Chang X, Yang Z, Bu D, Du J (2005) Modulating effect of hydrogen sulfide on gamma-aminobutyric acid B receptor in recurrent febrile seizures in rats. Neurosci Res 53:216–219

    Article  PubMed  CAS  Google Scholar 

  • Huang T, Solano J, He D, Loutfi M, Dietrich WD, Kuluz JW (2009) Traumatic injury activates MAP kinases in astrocytes: mechanisms of hypothermia and hyperthermia. J Neurotrauma 26:1535–1545

    Article  PubMed  Google Scholar 

  • Ignoul S, Eggermont J (2005) CBS domains: structure, function, and pathology in human proteins. Am J Physiol Cell Physiol 289:C1369–C1378

    Article  PubMed  CAS  Google Scholar 

  • Jeruc J, Vizjak A, Rozman B, Ferluga D (2006) Immunohistochemical expression of activated caspase-3 as a marker of apoptosis in glomeruli of human lupus nephritis. Am J Kidney Dis 48:410–418

    Article  PubMed  CAS  Google Scholar 

  • Kashiwamata S, Greenberg DM (1970) Studies on cystathionine synthase of rat liver. Properties of the highly purified enzyme. Biochim Biophys Acta 212:488–500

    Article  PubMed  CAS  Google Scholar 

  • Kashiwamata S, Kotake Y, Greenberg DM (1970) Studies of cystathionine synthase of rat liver: dissociation into two components by sodium dodecyl sulfate disc electrophoresis. Biochim Biophys Acta 212:501–503

    Article  PubMed  CAS  Google Scholar 

  • Kernie SG, Erwin TM, Parada LF (2001) Brain remodeling due to neuronal and astrocytic proliferation after controlled cortical injury in mice. J Neurosci Res 66:317–326

    Article  PubMed  CAS  Google Scholar 

  • Kimura H (2000) Hydrogen sulfide induces cyclic AMP and modulates the NMDA receptor. Biochem Biophys Res Commun 267:129–133

    Article  PubMed  CAS  Google Scholar 

  • Kimura H (2010) Hydrogen sulfide: from brain to gut. Antioxid Redox Signal 12:1111–1123

    Article  PubMed  CAS  Google Scholar 

  • Kraus J, Packman S, Fowler B, Rosenberg LE (1978) Purification and properties of cystathionine beta-synthase from human liver. Evidence for identical subunits. J Biol Chem 253:6523–6528

    PubMed  CAS  Google Scholar 

  • Kraus JP, Rosenberg LE (1983) Cystathionine beta-synthase from human liver: improved purification scheme and additional characterization of the enzyme in crude and pure form. Arch Biochem Biophys 222:44–52

    Article  PubMed  CAS  Google Scholar 

  • Lominadze D, Tyagi N, Sen U, Ovechkin A, Tyagi SC (2012) Homocysteine alters cerebral microvascular integrity and causes remodeling by antagonizing GABA-A receptor. Mol Cell Biochem. doi:10.1007/s11010-11012-11425-11015

  • Luo CL, Chen XP, Yang R, Sun YX, Li QQ, Bao HJ, Cao QQ, Ni H, Qin ZH, Tao LY (2010) Cathepsin B contributes to traumatic brain injury-induced cell death through a mitochondria-mediated apoptotic pathway. J Neurosci Res 88:2847–2858

    PubMed  CAS  Google Scholar 

  • Luo CL, Li BX, Li QQ, Chen XP, Sun YX, Bao HJ, Dai DK, Shen YW, Xu HF, Ni H, Wan L, Qin ZH, Tao LY, Zhao ZQ (2011) Autophagy is involved in traumatic brain injury-induced cell death and contributes to functional outcome deficits in mice. Neuroscience 184:54–63

    Article  PubMed  CAS  Google Scholar 

  • Maclean KN, Janosik M, Kraus E, Kozich V, Allen RH, Raab BK, Kraus JP (2002) Cystathionine beta-synthase is coordinately regulated with proliferation through a redox-sensitive mechanism in cultured human cells and Saccharomyces cerevisiae. J Cell Physiol 192:81–92

    Article  PubMed  CAS  Google Scholar 

  • Miles EW, Kraus JP (2004) Cystathionine beta-synthase: structure, function, regulation, and location of homocystinuria-causing mutations. J Biol Chem 279:29871–29874

    Article  PubMed  CAS  Google Scholar 

  • Nagai Y, Tsugane M, Oka J, Kimura H (2004) Hydrogen sulfide induces calcium waves in astrocytes. FASEB J 18:557–559

    PubMed  CAS  Google Scholar 

  • Pan LL, Liu XH, Gong QH, Yang HB, Zhu YZ (2012) Role of cystathionine gamma-lyase/hydrogen sulfide pathway in cardiovascular disease: a novel therapeutic strategy? Antioxid Redox Signal 17:106–118

    Article  PubMed  CAS  Google Scholar 

  • Pey AL, Majtan T, Sanchez-Ruiz JM, Kraus JP (2012) Human cystathionine beta-synthase (CBS) contains two classes of binding sites for S-adenosyl-l-methionine (SAM): complex regulation of CBS activity and stability by SAM. Biochem J. doi:10.1042/BJ20120731

  • Planque C, Dairou J, Noll C, Bui LC, Ripoll C, Guedj F, Delabar JM, Janel N (2012) Mice deficient in cystathionine beta synthase display increased Dyrk1A and SAHH activities in brain. J Mol Neurosci. doi:10.1007/s12031-12012-19835-12030

  • Qu K, Chen CP, Halliwell B, Moore PK, Wong PT (2006) Hydrogen sulfide is a mediator of cerebral ischemic damage. Stroke 37:889–893

    Article  PubMed  CAS  Google Scholar 

  • Raghupathi R, Graham DI, Mcintosh TK (2000) Apoptosis after traumatic brain injury. J Neurotrauma 17:927–938

    Article  PubMed  CAS  Google Scholar 

  • Regnier V, Billard JM, Gupta S, Potier B, Woerner S, Paly E, Ledru A, David S, Luilier S, Bizot JC, Vacano G, Kraus JP, Patterson D, Kruger WD, Delabar JM, London J (2012) Brain phenotype of transgenic mice overexpressing cystathionine beta-synthase. PLoS One 7:e29056

    Article  PubMed  CAS  Google Scholar 

  • Robert K, Vialard F, Thiery E, Toyama K, Sinet PM, Janel N, London J (2003) Expression of the cystathionine beta synthase (CBS) gene during mouse development and immunolocalization in adult brain. J Histochem Cytochem 51:363–371

    Article  PubMed  CAS  Google Scholar 

  • Shein NA, Grigoriadis N, Alexandrovich AG, Simeonidou C, Lourbopoulos A, Polyzoidou E, Trembovler V, Mascagni P, Dinarello CA, Shohami E (2009) Histone deacetylase inhibitor ITF2357 is neuroprotective, improves functional recovery, and induces glial apoptosis following experimental traumatic brain injury. FASEB J 23:4266–4275

    Article  PubMed  CAS  Google Scholar 

  • Talaei F, Bouma HR, Van Der Graaf AC, Strijkstra AM, Schmidt M, Henning RH (2011) Serotonin and dopamine protect from hypothermia/rewarming damage through the CBS/H2S pathway. PLoS One 6:e22568

    Article  PubMed  CAS  Google Scholar 

  • West MJ (1993) New stereological methods for counting neurons. Neurobiol Aging 14:275–285

    Article  PubMed  CAS  Google Scholar 

  • You Z, Savitz SI, Yang J, Degterev A, Yuan J, Cuny GD, Moskowitz MA, Whalen MJ (2008) Necrostatin-1 reduces histopathology and improves functional outcome after controlled cortical impact in mice. J Cereb Blood Flow Metab 28:1564–1573

    Article  PubMed  CAS  Google Scholar 

  • Zhang J, Xie Y, Xu Y, Shao C (2012a) Suppression of Endogenous hydrogen sulfide contributes to the radiation-induced bystander effects on hypoxic HepG2 cells. Radiat Res. doi:10.1667/RR2967.1661

  • Zhang M, Shan H, Gu Z, Wang D, Wang T, Wang Z, Tao L (2012b) Increased expression of calcium/calmodulin-dependent protein kinase type II subunit delta after rat traumatic brain injury. J Mol Neurosci 46:631–643

    Article  PubMed  CAS  Google Scholar 

  • Zhao JY, Yang XY, Shi KH, Sun SN, Hou J, Ye ZZ, Wang J, Duan WY, Qiao B, Chen YJ, Shen HB, Huang GY, Jin L, Wang HY (2012) A functional variant in the cystathionine beta-synthase gene promoter significantly reduces congenital heart disease susceptibility in a Han Chinese population. Cell Res. doi:10.1038/cr.2012.1135

  • Zhong WX, Wang YB, Peng L, Ge XZ, Zhang J, Liu SS, Zhang XN, Xu ZH, Chen Z, Luo JH (2012) Lanthionine synthetase C-like protein 1 interacts with and inhibits cystathionine beta-synthase: a target for neuronal antioxidant defense. J Biol Chem 287:34189–34201

    Article  PubMed  CAS  Google Scholar 

  • Zhou XH, Huang XL, Wei P, Tian FJ, Ling YL (2009) Role of hydrogen sulfide/cystathionine-gamma-lyase system in acute lung injury induced by lipopolysaccharide in rats. Zhongguo Wei Zhong Bing Ji Jiu Yi Xue 21:199–202

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 30872666, 81172911, and No. 81271379), Natural Science Foundation of Medical College of Nantong University (No. Y201003), The Priority Academic Program Development of Jiangsu Higher Education Institutions, and The Colleges and Universities in Jiangsu Province Plans to Graduate Research and Innovation (CXLX12_0824).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Xiping Chen or Luyang Tao.

Additional information

M. Zhang and H. Shan contributed equally to this work.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhang, M., Shan, H., Wang, Y. et al. The Expression Changes of Cystathionine-β-synthase in Brain Cortex After Traumatic Brain Injury. J Mol Neurosci 51, 57–67 (2013). https://doi.org/10.1007/s12031-012-9948-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12031-012-9948-5

Keywords

Navigation