Skip to main content

Advertisement

SpringerLink
Log in

l-Cysteine augments microtubule-associated protein 2 levels and enhances antioxidant activity in rats following traumatic brain injury

  • Original Article
  • Published:
3 Biotech Aims and scope Submit manuscript

Abstract

l-Cysteine is a well-known sulfur-containing non-essential amino acid that can be oxidized to cysteine, which possesses a variety of pharmacological actions, including antioxidant and anti-inflammatory activities. Traumatic brain injury (TBI) is defined as a closed head injury that leads to temporary alterations in neural function and further leads to pathophysiological processes. In the present study, rats were categorized into sham, control, 100 mg/kg l-cysteine, and 200 mg/kg l-cysteine groups and then the levels of lipid peroxidation, reduced glutathione (GSH), catalase, superoxide dismutase (SOD), reactive oxygen species (ROS), and mRNA and protein expression of microtubule-associated protein 2 (MAP2) were determined. Following supplementation with l-cysteine, there were reductions in lipid peroxidation and ROS levels, whereas catalase, SOD, and GSH levels increased. Additionally, the mRNA expression of MAP2 in the control rats was drastically reduced by 67% compared to the sham rats. However, supplementation with 100 mg/kg of l-cysteine and 200 mg/kg of l-cysteine significantly increased MAP2 mRNA expression by 84.8% and 169.7%, respectively. Similarly, MAP2 protein expression was drastically reduced by 61% in control rats compared to sham rats, but supplementation with 100 mg/kg of l-cysteine and 200 mg/kg of l-cysteine significantly increased MAP2 protein expression by 41% and 94.9%, respectively. Taken together, these data suggest that supplementation with l-cysteine significantly reduced lipid peroxidation and ROS levels, but increased antioxidant levels and the mRNA and protein expression of MAP2 in rats following TBI.

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

Access this article

Log in via an institution

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

Similar content being viewed by others

References

  • Arnér ES, Holmgren A (2006) The thioredoxin system in cancer. Semin Cancer Biol 16(6):420–426

    Article  Google Scholar 

  • Balic M, Rapp N, Stanzer S, Lin H, Strutz J, Szkandera J, Daidone MG, Samonigg H, Cote RJ, Dandachi N (2011) Novel immunofluorescence protocol for multimarker assessment of putative disseminating breast cancer stem cells. Appl Immunohistochem Mol Morphol 19:33–40

    Article  CAS  Google Scholar 

  • Bavarsad Shahripour R, Harrigan MR, Alexandrov AV (2014) N-acetylcysteine (NAC) in neurological disorders: mechanisms of action and therapeutic opportunities. Brain Behav 4(2):108–122

    Article  Google Scholar 

  • Baydas G, Gursu MF, Yilmaz S, Canpolat S, Yasar A, Cikim G, Canatan H (2002) Daily rhythm of glutathione peroxidase activity, lipid peroxidation and glutathione levels in tissues of pinealectomized rats. Neurosci Lett 323:195–198

    Article  CAS  Google Scholar 

  • Bobyn PJ, Franklin JL, Wall CM, Thornhill JA, Juurlink BH, Paterson PG (2002) The effects of dietary sulfur amino acid deficiency on rat brain glutathione concentration and neural damage in global, hemispheric hypoxia-ischemia. Nutr Neurosci 5(6):407–416

    Article  CAS  Google Scholar 

  • Buddle M, Eberhardt E, Ciminello LH, Levin T, Wing R, DiPasquale K, Raley-Susman KM (2003) Microtubule-associated protein 2 (MAP2) associates with the NMDA receptor and is spatially redistributed within rat hippocampal neurons after oxygen-glucose deprivation. Brain Res 978(1–2):38–50

    Article  CAS  Google Scholar 

  • Carbone DL, Doorn JA, Kiebler Z, Petersen DR (2005) Cysteine modification by lipid peroxidation products inhibits protein disulfide isomerase. Chem Res Toxicol 18(8):1324–1331

    Article  CAS  Google Scholar 

  • d’Hemecourt P (2011) Subacute symptoms of a sports-related concussion: outpatient management and return to play. Clin Sports Med 30:63–72

    Article  Google Scholar 

  • Dilger RN, Toue S, Kimura T, Sakai R, Baker DH (2007) Excess dietary l-cysteine, but not l-cystine, is lethal for chicks but not for rats or pigs. J Nutr 137(2):331–338

    Article  CAS  Google Scholar 

  • Eakin K, Baratz-Goldstein R, Pick CG, Zindel O, Balaban CD, Hoffer ME, Lockwood M, Miller J, Hoffer BJ (2014) Efficacy of N-acetyl cysteine in traumatic brain injury. PLoS One 9(4):e90617

    Article  Google Scholar 

  • Elias RJ, McClements DJ, Decker EA (2005) Antioxidant activity of cysteine, tryptophan, and methionine residues in continuous phase beta-lactoglobulin in oil-in-water emulsions. J Agric Food Chem 53(26):10248–10253

    Article  CAS  Google Scholar 

  • Fechter LD, Nelson-Miller A, Gearhart C (2008) Depletion of liver glutathione levels in rats: a potential confound of nose-only inhalation. Inhal Toxicol 20(9):885–890

    Article  CAS  Google Scholar 

  • Fontaine-Lenoir V, Chambraud B, Fellous A, David S, Duchossoy Y, Baulieu EE, Robel P (2006) Microtubule-associated protein 2 (MAP2) is a neurosteroid receptor. Proc Natl Acad Sci USA 103(12):4711–4716

    Article  CAS  Google Scholar 

  • Hasegawa S, Ichiyama T, Sonaka I, Ohsaki A, Okada S, Wakiguchi H, Kudo K, Kittaka S, Hara M, Furukawa S (2012) Cysteine, histidine and glycine exhibit anti-inflammatory effects in human coronary arterial endothelial cells. Clin Exp Immunol 167(2):269–274

    Article  CAS  Google Scholar 

  • Higashikata T, Yamagishi M, Sasaki H, Minatoya K, Ogino H, Ishibashi-Ueda H, Hao H, Nagaya N, Tomoike H, Sakamoto A (2004) Application of real-time RT-PCR to quantifying gene expression of matrix metalloproteinases and tissue inhibitors of metalloproteinases in human abdominal aortic aneurysm. Atherosclerosis 177:353–360

    Article  CAS  Google Scholar 

  • Hoffer BJ, Pick CG, Hoffer ME, Becker RE, Chiang YH, Greig NH (2017) Repositioning drugs for traumatic brain injury-N-acetyl cysteine and Phenserine. J Biomed Sci 9 24(1):71

    Article  Google Scholar 

  • Jain SK, Kanikarla-Marie P, Warden C, Micinski D (2016) l-cysteine supplementation upregulates glutathione (GSH) and vitamin D binding protein (VDBP) in hepatocytes cultured in high glucose and in vivo in the liver, and increases blood levels of GSH, VDBP, and 25-hydroxy-vitamin D in Zucker diabetic fatty rats. Mol Nutr Food Res 60(5):1090–1098

    Article  CAS  Google Scholar 

  • Jordão AA, Chiarello PG, Arantes MR, Meirelles MS, Vannucchi H (2004) Effect of an acute dose of ethanol on lipid peroxidation in rats: the action of vitamin E. Food Chem Toxicol 42:459–464

    Article  Google Scholar 

  • Karanth J, Jeevaratnam K (2005) Oxidative stress and antioxidant status in rat blood, liver and muscle: effect of dietary lipid, carnitine, and exercise. Int J Vitam Nutr Res 75(5):333–339

    Article  CAS  Google Scholar 

  • Kim HJ, Han SJ (2017) A simple rat model of mild traumatic brain injury: a device for reproducing anatomical and neurological changes of mild traumatic brain injury. PeerJ 5:e2818

    Article  Google Scholar 

  • Landino LM, Skreslet TE, Alston JA (2004) Cysteine oxidation of tau and microtubule-associated protein-2 by peroxynitrite: modulation of microtubule assembly kinetics by the thioredoxin reductase system. J Biol Chem 279(33):35101–35105

    Article  CAS  Google Scholar 

  • Lee S, Han KH, Nakamura Y, Kawakami S, Shimada K, Hayakawa T, Onoue H, Fukushima M (2013) Dietary l-cysteine improves the antioxidative potential and lipid metabolism in rats fed a normal diet. Biosci Biotechnol Biochem 77(7):1430–1434

    Article  CAS  Google Scholar 

  • Li J, Xu L, Deng X, Jiang C, Pan C, Chen L, Han Y, Dai W, Hu L, Zhang G, Cheng Z, Liu W (2016) N-acetyl-cysteine attenuates neuropathic pain by suppressing matrix metalloproteinases. Pain 157(8):1711–1723

    Article  CAS  Google Scholar 

  • Miura Y, Honda S, Masuda A, Masuda T (2014) Antioxidant activities of cysteine derivatives against lipid oxidation in anhydrous media. Biosci Biotechnol Biochem 78(8):1452–1455

    Article  CAS  Google Scholar 

  • Miyazawa T, Bonnekoh P, Hossman KA (1993) Temperature effect on immunostaining of microtubule-associated protein 2 and synaptophysin after 30 minutes of forebrain ischemia in rat, Acta. Neuropathol 85:526–532

    CAS  Google Scholar 

  • Roesslein M, Hirsch C, Kaiser JP, Krug HF, Wick P (2013) Comparability of in vitro tests for bioactive nanoparticles: a common assay to detect reactive oxygen species as an example. Int J Mol Sci 14(12):24320–24337

    Article  Google Scholar 

  • Ruff RM (2011) Mild traumatic brain injury and neural recovery: rethinking the debate. NeuroRehabilitation 28:167–180

    PubMed  Google Scholar 

  • Saleh AAS (2015) Anti-neuroinflammatory and antioxidant effects of N-acetyl cysteine in long-term consumption of artificial sweetener aspartame in the rat cerebral cortex. J Basic Appl Zool 72:73–80

    Article  CAS  Google Scholar 

  • Saravanan N, Senthil D, Varalakshmi P (1995) Effect of L-cysteine on lipid peroxidation in experimental urolithiatic rats. Pharmacol Res 32(3):165–169

    Article  CAS  Google Scholar 

  • Xiong Y, Mahmood A, Chopp M (2013) Animal models of traumatic brain injury. Nat Rev Neurosci 14(2):128–142

    Article  CAS  Google Scholar 

  • Ye S, Dong J, Han B (2010) Protective effect of reduced glutathione and venous systemic oxygen persufflation on rat steatotic graft following liver transplantation. J Surg Res 158:138–146

    Article  CAS  Google Scholar 

Download references

Acknowledgement

This study was supported by National Natural Sciences Foundation of China (Grant No.81801721).

Author information

Authors and Affiliations

  1. Department of Neurosurgery, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China

    Zhu Ouyang & Yugang Jiang

  2. Department of Ultrasound Diagnosis, The Second Xiangya Hospital of Central South University, Changsha, 410011, Hunan, China

    Ganqiong Xu

Authors
  1. Zhu Ouyang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ganqiong Xu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yugang Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Yugang Jiang.

Ethics declarations

Conflict of interest

Authors declare that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ouyang, Z., Xu, G. & Jiang, Y. l-Cysteine augments microtubule-associated protein 2 levels and enhances antioxidant activity in rats following traumatic brain injury. 3 Biotech 9, 280 (2019). https://doi.org/10.1007/s13205-019-1805-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s13205-019-1805-6

Keywords

Search

Navigation