Skip to main content

Advertisement

Log in

Neuroprotective Effects of 2-Cyclopropylimino-3-Methyl-1,3-Thiazoline Hydrochloride Against Oxidative Stress

  • Short Communication
  • Published:
Cellular and Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Oxidative stress, glutamate excitotoxicity, and inflammation are the important pathological mechanisms in neurodegenerative diseases. Recently, we reported that 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride protects rat glial cells against glutamate-induced excitotoxicity. In this study, we report the effects of 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride on primary cultured cortical astrocytes after exposure to hydrogen peroxide (H2O2). Pretreatment of cells with 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride prior to H2O2 exposure attenuated the H2O2-induced reductions in cell survival and superoxide dismutase, catalase, glutathione, and glutathione peroxidase activities. It also reduced H2O2-induced increases in reactive oxygen species levels, malondialdehyde content, and production of nitric oxide. These effects were all concentration-dependent. Our results suggest that 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride protects against oxidative stress.

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.

Fig. 1
Fig. 2

References

  • Aebi H (1984) Catalase in vitro. Methods Enzymol 105:121–126

    Article  PubMed  CAS  Google Scholar 

  • Beal MF, Hyman BT, Koroshetz W (1993) Do defects in mitochondrial energy metabolism underlie the pathology of neurodegenerative diseases? Trends Neurosci 16:125–131

    Article  PubMed  CAS  Google Scholar 

  • Brantley E, Antony S, Kohlhagen G, Meng LH, Agama K, Stinson SF, Sausville EA, Pommier Y (2006) Anti-tumor drug candidate 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole induces single-strand breaks and DNA-protein cross-links in sensitive MCF-7 breast cancer cells. Cancer Chemother Pharmacol 58:62–72

    Article  PubMed  CAS  Google Scholar 

  • Carboni S, Hiver A, Szyndralewiez C, Gaillard P, Gotteland JP, Vitte PA (2004) AS601245 (1,3-benzothiazol-2-yl (2-[[2-(3-pyridinyl) ethyl] amino]-4 pyrimidinyl) acetonitrile): a c-Jun NH2-terminal protein kinase inhibitor with neuroprotective properties. J Pharmacol Exp Ther 310:25–32

    Article  PubMed  CAS  Google Scholar 

  • Chan PH (1996) Role of oxidants in ischemic brain damage. Stroke 27:1124–1129

    Article  PubMed  CAS  Google Scholar 

  • Choi MM, Kim EA, Hahn HG, Nam KD, Yang SJ, Choi SY, Kim TU, Cho SW, Huh JW (2007) Protective effect of benzothiazole derivative KHG21834 on amyloid beta-induced neurotoxicity in PC12 cells and cortical and mesencephalic neurons. Toxicology 239:156–166

    Article  PubMed  CAS  Google Scholar 

  • Ciccarelli R, D’Alimonte I, Ballerini P, D’Auro M, Nargi E, Buccella S, Di Iorio P, Bruno V, Nicoletti F, Caciagli F (2007) Molecular signalling mediating the protective effect of A1 adenosine and mGlu3 metabotropic glutamate receptor activation against apoptosis by oxygen/glucose deprivation in cultured astrocytes. Mol Pharmacol 71:1369–1380

    Article  PubMed  CAS  Google Scholar 

  • Clementi E, Vecchio I, Corasaniti MT, Nistico G (1995) Nitro oxide modulates agonist-evoked Ca2+ release and influx responses in PC12-64 cells. Eur J Pharmacol 289:113–123

    Article  PubMed  CAS  Google Scholar 

  • Dawson DA, Graham DI, McCulloch J, Macrae IM (1994) Anti-ischaemic efficacy of a nitric oxide synthase inhibitor and a N-methyl-d-aspartate receptor antagonist in models of transient and permanent focal cerebral ischaemia. Br J Pharmacol 113:247–253

    PubMed  CAS  Google Scholar 

  • Dore S, Otsuka T, Mito T, Sugo N, Hand T, Wu L, Hurn PD, Traystman RJ, Andreasson K (2003) Neuronal overexpression of cyclooxygenase-2 increases cerebral infarction. Ann Neurol 5:155–162

    Article  Google Scholar 

  • Fallarini S, Miglio G, Paoletti T, Minassi A, Amoruso A, Bardelli C, Brunelleschi S, Lombardi G (2009) Clovamide and rosmarinic acid induce neuroprotective effects in in vitro models of neuronal death. Br J Pharmacol 15:1072–1084

    Article  Google Scholar 

  • Flohe L, Ginzler WA (1984) Assay of glutathione peroxidase. Methods Enzymol 105:114–121

    Article  PubMed  CAS  Google Scholar 

  • Giorgio M, Trinei M, Migliaccio E, Pelicci PG (2007) Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? Nat Rev Mol Cell Biol 8:722–728

    Article  PubMed  CAS  Google Scholar 

  • Halliwell B (1992) Reactive oxygen species and the central nervous system. J Neurochem 59:1609–1623

    Article  PubMed  CAS  Google Scholar 

  • Heiser V, Engemann S, Brocker W, Dunkel I, Boeddrich A, Waelter S, Nordhoff E, Lurz R, Schugardt N, Rautenberg S, Herhaus C, Barnickel G, Bottcher H, Lehrach H, Wanker EE (2002) Identification of benzothiazoles as potential polyglutamine aggregation inhibitors of Huntington’s disease by using an automated filter retardation assay. Proc Natl Acad Sci USA 99:16400–16406

    Article  PubMed  CAS  Google Scholar 

  • Herson PS, Lee K, Pinnock RD, Hughes J, Ashford ML (1999) Hydrogen peroxide induces intracellular calcium overload by activation of a non-selective cation channel in an insulin-secreting cell line. J Biol Chem 274:833–841

    Article  PubMed  CAS  Google Scholar 

  • Ishiyama T, Okada R, Nishibe H, Mitsumoto H, Nakayama C (2004) Riluzole slows the progression of neuromuscular dysfunction in the wobbler mouse motor neuron disease. Brain Res 1019:226–236

    Article  PubMed  CAS  Google Scholar 

  • Ji BS, Gao Y (2008) Protective effect of trihexyphenidyl on hydrogen peroxide-induced oxidative damage in PC12 cells. Neurosci Lett 437:50–54

    Article  PubMed  CAS  Google Scholar 

  • Kim DW, Kim SY, Lee SH, Lee YP, Lee MJ, Jeong MS, Jang SH, Park J, Lee KS, Kang TC, Won MH, Cho SW, Kwon OS, Eum WS, Choi SY (2008) Protein transduction of an antioxidant enzyme: subcellular localization of superoxide dismutase fusion protein in cells. BMB Rep 41:170–175

    Article  PubMed  Google Scholar 

  • Kim DW, Jeong HJ, Kang HW, Shin MJ, Sohn EJ, Kim MJ, Ahn EH, An JJ, Jang SH, Yoo KY, Won MH, Kang TC, Hwang IK, Kwon OS, Cho S-W, Park J, Eum WS, Choi SY (2009) Transduced human PEP-1-catalase fusion protein attenuates ischemic neuronal damage. Free Radic Biol Med 47:941–952

    Article  PubMed  CAS  Google Scholar 

  • Kim E-A, Hahn H-G, Kim KS, Kim TU, Choi SY, Cho S-W (2010a) Suppression of glutamate-induced excitotoxicity by 2-cyclopropylimino-3-methyl-1,3-thiazoline hydrochloride in rat glial cultures. Cell Mol Neurobiol 30:807–815

    Article  PubMed  CAS  Google Scholar 

  • Kim E-A, Hahn H-G, Kim TU, Choi SY, Cho S-W (2010b) Attenuation of β-amyloid-induced neuroinflammation by KHG21834 in vivo. BMB Rep 43:413–418

    Article  PubMed  CAS  Google Scholar 

  • Kim E-A, Kim H, Ahn J-Y, Hahn H-G, Kim K-S, Kim TU, Cho S-W (2010c) Suppression of lipopolysaccharide-induced microglial activation by a benzothiazole derivative. Mol Cells 30:51–57

    Article  PubMed  CAS  Google Scholar 

  • Kowara R, Moraleja KL, Chakravarthy B (2006) Involvement of nitro oxide sythase and ROS-mediated activation of L-type voltage-gated Ca2+ channel in NMDA-induced DPYSL3 degradation. Brain Res 1119:40–49

    Article  PubMed  CAS  Google Scholar 

  • Liu D, Smith CL, Barone FC, Ellison JA, Lysko PG, Li K, Simpson IA (1999) Astrocytic demise precedes delayed neuronal death in focal ischemic rat brain. Mol Brain Res 68:29–41

    Article  PubMed  CAS  Google Scholar 

  • Lombardi G, Varsaldi F, Miglio G, Papini MG, Battaglia A, Canonico PL (2002) Cabergoline prevents necrotic neuronal death in an in vitro model of oxidative stress. Eur J Pharmacol 457:95–99

    Article  PubMed  CAS  Google Scholar 

  • Maheshwari A, Misro MM, Aggarwal A, Sharma RK, Nandan D (2009) Pathways involved in testicular germ cell apoptosis induced by H2O2 in vitro. FEBS J 276:870–881

    Article  PubMed  CAS  Google Scholar 

  • Mortimer CG, Wells G, Crochard JP, Stone EL, Bradshaw TD, Stevens MFG, Westwell AD (2006) Antitumor benzothiazoles. 26.1 2-(3,4-dimethoxyphenyl)-5-fluorobenzothiazole (GW 610, NSC 721648), a simple fluorinated 2-arylbenzothiazole, shows potent and selective inhibitory activity against lung, colon, and breast cancer cell lines. J Med Chem 49:179–185

    Article  PubMed  CAS  Google Scholar 

  • Piantadosi CA, Zhang J (1996) Mitochondrial generation of reactive oxygen species after brain ischemia in the rat. Stroke 27:327–331

    Article  PubMed  CAS  Google Scholar 

  • Pietrancosta N, Moumen A, Dono R, Lingor P, Planchamp V, Lamballe F, Bahr M, Kraus JL, Maina F (2006) Imino-tetrahydro-benzothiazole derivatives as p53 inhibitors: discovery of a highly potent in vivo inhibitor and its action mechanism. J Med Chem 49:3645–3652

    Article  PubMed  CAS  Google Scholar 

  • Qureshi GA, Baig S, Sarwar M, Parvez SH (2004) Neurotoxicity, oxidative stress and cerebrovascular disorders. Neurotoxicology 25:121–138

    Article  PubMed  CAS  Google Scholar 

  • Sayre LM, Perry G, Smith MA (2008) Oxidative stress and neurotoxicity. Chem Res Toxicol 21:172–188

    Article  PubMed  Google Scholar 

  • Simonian NA, Coyle JT (1996) Oxidative stress in neurodegenerative diseases. Annu Rev Pharmacol Toxicol 36:83–106

    Article  PubMed  CAS  Google Scholar 

  • Suzuki Y, Takahashi H, Fukuda M, Hino H, Kobayashi K, Tanaka J, Ishii E (2009) β-Hydroxybutyrate alters GABA-transaminase activity in cultured astrocytes. Brain Res 1268:17–23

    Article  PubMed  CAS  Google Scholar 

  • Trushina E, McMurray CT (2007) Oxidative stress and mitochondrial dysfunction in neurodegenerative diseases. Neuroscience 145:1233–1248

    Article  PubMed  CAS  Google Scholar 

  • Urbani A, Belluzzi O (2000) Riluzole inhibits the persistent sodium current in mammalian CNS neurons. Eur J Neurosci 12:3567–3574

    Article  PubMed  CAS  Google Scholar 

  • Vieira HL, Belzacq AS, Haouzi D (2001) The adenine nucleotide translocator: a target of nitric oxide, peroxynitrite, and 4-hydroxynonenal. Oncogene 20:4305–4316

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009-0073270 & 2010-0016830), by the Asan Institute for Life Sciences (2009-010), and by a Student Research Grant of the University of Ulsan College of Medicine, Seoul, Korea.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Sung-Woo Cho.

Additional information

Hanwook Kim, Hyo Jeong Son, and Seung Cheol Ha contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, H., Son, H.J., Ha, S.C. et al. Neuroprotective Effects of 2-Cyclopropylimino-3-Methyl-1,3-Thiazoline Hydrochloride Against Oxidative Stress. Cell Mol Neurobiol 31, 979–984 (2011). https://doi.org/10.1007/s10571-011-9713-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10571-011-9713-2

Keywords

Navigation