Skip to main content

Advertisement

SpringerLink
Log in

Neuroprotective Effect of the Novel Compound ITH33/IQM9.21 Against Oxidative Stress and Na+ and Ca2+ Overload in Motor Neuron-like NSC-34 Cells

  • Original Article
  • Published:
Neurotoxicity Research Aims and scope Submit manuscript

Abstract

Alternatives for the treatment of amyotrophic lateral sclerosis (ALS) are scarce and controversial. The etiology of neuronal vulnerability in ALS is being studied in motor neuron-like NSC-34 cells to determine the underlying mechanisms leading to selective loss of motor neurons. One such mechanism is associated with mitochondrial oxidative stress, Ca2+ overload, and low expression of Ca2+-buffering proteins. Therefore, in order to elicit neuronal death in ALS, NSC-34 cells were exposed to the following cytotoxic agents: (1) a mixture of oligomycin 10 µM and rotenone 30 µM (O/R), or (2) phenylarsine oxide 1 µM (PAO) (to mimic excess free radical production during mitochondrial dysfunction), and (3) veratridine 100 µM (VTD) (to induce overload of Na+ and Ca2+ and to alter distribution of Ca2+-buffering proteins [parvalbumin and calbindin-D28k]). Thus, the aim of the study was to test the novel neuroprotective compound ITH33/IQM9.21 (ITH33) and to compare it with riluzole on in vitro models of neurotoxicity. Cell viability measured with MTT showed that only ITH33 protected against O/R at 3 μM and PAO at 10 μM, but not riluzole. ITH33 and riluzole were neuroprotective against VTD, blocked the maximum peak and the number of [Ca2+]c oscillations per cell, and restored the effect on parvalbumin. However, only riluzole reversed the effect on calbindin-D28k levels. Therefore, ITH33 was neuroprotective against oxidative stress and Na+/Ca2+ overload, both of which are involved in ALS.

Graphical Abstract

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
Fig. 6

Similar content being viewed by others

Abbreviations

AFU:

Arbitrary fluorescence units

ALS:

Amyotrophic lateral sclerosis

AMPA:

Alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid

ATP:

Adenosine triphosphate

BBB:

Blood–brain barrier

BCC:

Bovine chromaffin cell

[Ca2+]c :

Cytosolic concentration of Ca2+

DAPI:

4′,6-diamidino-2-phenylindole

DMEM:

Dulbecco’s minimal essential medium

ITH33:

ITH33/IQM9.21

DMSO:

Dimethyl sulfoxide

EAAT2:

Excitatory amino acid transporter type 2

FBS:

Fetal bovine serum

mPTP:

Mitochondrial permeability transition pore

MTT:

Bromide (3-[4, 5-dimethylthiazol-2-yl]-2, 5-diphenyl)

NMDA:

N-methyl-d-aspartate

O/R:

Oligomycin and rotenone

OD:

Optical density

PAO:

Phenylarsine oxide

PBS:

Phosphate-buffered saline

Peakmax :

Maximum peak

Ril:

Riluzole

ROS:

Reactive oxygen species

RT:

Room temperature

SOD1:

Cu2+/Zn2+-superoxide dismutase

VDCC:

Voltage-dependent Ca2+ channels

VTD:

Veratridine

References

  • Aguilar J-LGd, Echaniz-Laguna A, Fergani A, René F, Meininger V, Loeffler J-P, Dupuis L (2007) Amyotrophic lateral sclerosis: all roads lead to Rome. J Neurochem 101:1153–1160

    Article  Google Scholar 

  • Alexianu ME, Ho BK, Mohamed AH, La Bella V, Smith RG, Appel SH (1994) The role of calcium-binding proteins in selective motoneuron vulnerability in amyotrophic lateral sclerosis. Ann Neurol 36:846–858

    Article  CAS  PubMed  Google Scholar 

  • Appel SH, Beers D, Siklos L, Engelhardt JI, Mosier DR (2001) Calcium: the darth vader of ALS. Amyotroph Lateral Scler Other Motor Neuron Disord 2(Suppl 1):S47–S54

    CAS  PubMed  Google Scholar 

  • Arce MP, Rodriguez-Franco MI, Gonzalez-Munoz GC, Perez C, Lopez B, Villarroya M, Lopez MG, Garcia AG, Conde S (2009) Neuroprotective and cholinergic properties of multifunctional glutamic acid derivatives for the treatment of Alzheimer’s disease. J Med Chem 52:7249–7257

    Article  CAS  PubMed  Google Scholar 

  • Bellingham MC (2011) A review of the neural mechanisms of action and clinical efficiency of riluzole in treating amyotrophic lateral sclerosis: what have we learned in the last decade? CNS Neurosci Ther 17:4–31

    Article  CAS  PubMed  Google Scholar 

  • Benoit E, Escande D (1991) Riluzole specifically blocks inactivated Na channels in myelinated nerve fibre. Pflugers Arch 419:603–609

    Article  CAS  PubMed  Google Scholar 

  • Bezprozvanny I (2009) Calcium signaling and neurodegenerative diseases. Trends Mol Med 15:89–100

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Borthwick GM, Johnson MA, Ince PG, Shaw PJ, Turnbull DM (1999) Mitochondrial enzyme activity in amyotrophic lateral sclerosis: implications for the role of mitochondria in neuronal cell death. Ann Neurol 46:787–790

    Article  CAS  PubMed  Google Scholar 

  • Buttke TM, Sandstrom PA (1994) Oxidative stress as a mediator of apoptosis. Immunol Today 15:7–10

    Article  CAS  PubMed  Google Scholar 

  • Cano-Abad MF, Lopez MG, Hernandez-Guijo JM, Zapater P, Gandia L, Sanchez-Garcia P, Garcia AG (1998) Effects of the neuroprotectant lubeluzole on the cytotoxic actions of veratridine, barium, ouabain and 6-hydroxydopamine in chromaffin cells. Br J Pharmacol 124:1187–1196

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cano-Abad MF, Villarroya M, Garcia AG, Gabilan NH, Lopez MG (2001) Calcium entry through L-type calcium channels causes mitochondrial disruption and chromaffin cell death. J Biol Chem 276:39695–39704

    Article  CAS  PubMed  Google Scholar 

  • Carri MT, Ferri A, Battistoni A, Famhy L, Gabbianelli R, Poccia F, Rotilio G (1997) Expression of a Cu, Zn superoxide dismutase typical of familial amyotrophic lateral sclerosis induces mitochondrial alteration and increase of cytosolic Ca2+ concentration in transfected neuroblastoma SH-SY5Y cells. FEBS Lett 414:365–368

    Article  CAS  PubMed  Google Scholar 

  • Catterall WA, Coppersmith J (1981) Pharmacological properties of sodium channels in cultured rat heart cells. Mol Pharmacol 20:533–542

    CAS  PubMed  Google Scholar 

  • Celio MR (1990) Calbindin D-28k and parvalbumin in the rat nervous system. Neuroscience 35:375–475

    Article  CAS  PubMed  Google Scholar 

  • Chen WC, Cheng HH, Huang CJ, Chou CT, Liu SI, Chen IS, Hsu SS, Chang HT, Huang JK, Jan CR (2006) Effect of riluzole on Ca2+ movement and cytotoxicity in Madin-Darby canine kidney cells. Hum Exp Toxicol 25:461–469

    Article  CAS  PubMed  Google Scholar 

  • Conceicao IM, Lebrun I, Cano-Abad M, Gandia L, Hernandez-Guijo JM, Lopez MG, Villarroya M, Jurkiewicz A, Garcia AG (1998) Synergism between toxin-gamma from Brazilian scorpion Tityus serrulatus and veratridine in chromaffin cells. Am J Physiol 274:C1745–C1754

    CAS  PubMed  Google Scholar 

  • Dhaliwal GK, Grewal RP (2000) Mitochondrial DNA deletion mutation levels are elevated in ALS brains. NeuroReport 11:2507–2509

    Article  CAS  PubMed  Google Scholar 

  • Dimitriadi M, Kye MJ, Kalloo G, Yersak JM, Sahin M, Hart AC (2013) The neuroprotective drug riluzole acts via small conductance Ca2+-activated K+ channels to ameliorate defects in spinal muscular atrophy models. J Neurosci 33:6557–6562

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Egea J, Rosa AO, Cuadrado A, Garcia AG, Lopez MG (2007) Nicotinic receptor activation by epibatidine induces heme oxygenase-1 and protects chromaffin cells against oxidative stress. J Neurochem 102:1842–1852

    Article  CAS  PubMed  Google Scholar 

  • German DC, Ng MC, Liang CL, McMahon A, Iacopino AM (1997) Calbindin-D28k in nerve cell nuclei. Neuroscience 81:735–743

    Article  CAS  PubMed  Google Scholar 

  • Gros-Louis F, Gaspar C, Rouleau GA (2006) Genetics of familial and sporadic amyotrophic lateral sclerosis. Biochim Biophys Acta 1762:956–972

    Article  CAS  PubMed  Google Scholar 

  • Hebert T, Drapeau P, Pradier L, Dunn RJ (1994) Block of the rat brain IIA sodium channel alpha subunit by the neuroprotective drug riluzole. Mol Pharmacol 45:1055–1060

    CAS  PubMed  Google Scholar 

  • Heizmann CW, Braun K (1992) Changes in Ca(2+)-binding proteins in human neurodegenerative disorders. Trends Neurosci 15:259–264

    Article  CAS  PubMed  Google Scholar 

  • Hmadcha A, Carballo M, Conde M, Marquez G, Monteseirin J, Martin-Nieto J, Bedoya FJ, Pintado E, Sobrino F (1999) Phenylarsine oxide increases intracellular calcium mobility and inhibits Ca(2+)-dependent ATPase activity in thymocytes. Mol Genet Metab 68:363–370

    Article  CAS  PubMed  Google Scholar 

  • Hoglinger GU, Lannuzel A, Khondiker ME, Michel PP, Duyckaerts C, Feger J, Champy P, Prigent A, Medja F, Lombes A, Oertel WH, Ruberg M, Hirsch EC (2005) The mitochondrial complex I inhibitor rotenone triggers a cerebral tauopathy. J Neurochem 95:930–939

    Article  CAS  PubMed  Google Scholar 

  • Huang CS, Song JH, Nagata K, Yeh JZ, Narahashi T (1997) Effects of the neuroprotective agent riluzole on the high voltage-activated calcium channels of rat dorsal root ganglion neurons. J Pharmacol Exp Ther 282:1280–1290

    CAS  PubMed  Google Scholar 

  • Ince P, Stout N, Shaw P, Slade J, Hunziker W, Heizmann CW, Baimbridge KG (1993) Parvalbumin and calbindin D-28k in the human motor system and in motor neuron disease. Neuropathol Appl Neurobiol 19:291–299

    Article  CAS  PubMed  Google Scholar 

  • Kawamata H, Manfredi G (2010) Mitochondrial dysfunction and intracellular calcium dysregulation in ALS. Mech Ageing Dev 131:517–526

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kononenko NI, Shao LR, Dudek FE (2004) Riluzole-sensitive slowly inactivating sodium current in rat suprachiasmatic nucleus neurons. J Neurophysiol 91:710–718

    Article  CAS  PubMed  Google Scholar 

  • Kruman I, Bruce-Keller AJ, Bredesen D, Waeg G, Mattson MP (1997) Evidence that 4-hydroxynonenal mediates oxidative stress-induced neuronal apoptosis. J Neurosci 17:5089–5100

    CAS  PubMed  Google Scholar 

  • Lamanauskas N, Nistri A (2008) Riluzole blocks persistent Na+ and Ca2+ currents and modulates release of glutamate via presynaptic NMDA receptors on neonatal rat hypoglossal motoneurons in vitro. Eur J Neurosci 27:2501–2514

    Article  PubMed  Google Scholar 

  • Lopez MG, Artalejo AR, Garcia AG, Neher E, Garcia-Sancho J (1995) Veratridine-induced oscillations of cytosolic calcium and membrane potential in bovine chromaffin cells. J Physiol 482(Pt 1):15–27

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lorrio S, Gomez-Rangel V, Negredo P, Egea J, Leon R, Romero A, Dal-Cim T, Villarroya M, Rodriguez-Franco MI, Conde S, Arce MP, Roda JM, Garcia AG, Lopez MG (2013) Novel multitarget ligand ITH33/IQM9.21 provides neuroprotection in in vitro and in vivo models related to brain ischemia. Neuropharmacology 67:403–411

    Article  CAS  PubMed  Google Scholar 

  • Maroto R, De la Fuente MT, Artalejo AR, Abad F, Lopez MG, Garcia-Sancho J, Garcia AG (1994) Effects of Ca2+ channel antagonists on chromaffin cell death and cytosolic Ca2+ oscillations induced by veratridine. Eur J Pharmacol 270:331–339

    CAS  PubMed  Google Scholar 

  • Maroto R, de la Fuente MT, Zapater P, Abad F, Esquerro E, Garcia AG (1996) Effects of omega-conotoxin MVIIC on veratridine-induced cytotoxicity and cytosolic Ca(2+) oscillations. Brain Res 714:209–214

    Article  CAS  PubMed  Google Scholar 

  • Maroto M, de Diego AM, Albinana E, Fernandez-Morales JC, Caricati-Neto A, Jurkiewicz A, Yanez M, Rodriguez-Franco MI, Conde S, Arce MP, Hernandez-Guijo JM, Garcia AG (2011) Multi-target novel neuroprotective compound ITH33/IQM9.21 inhibits calcium entry, calcium signals and exocytosis. Cell Calcium 50:359–369

    Article  CAS  PubMed  Google Scholar 

  • Martin D, Thompson MA, Nadler JV (1993) The neuroprotective agent riluzole inhibits release of glutamate and aspartate from slices of hippocampal area CA1. Eur J Pharmacol 250:473–476

    Article  CAS  PubMed  Google Scholar 

  • Mattiazzi M, D’Aurelio M, Gajewski CD, Martushova K, Kiaei M, Beal MF, Manfredi G (2002) Mutated human SOD1 causes dysfunction of oxidative phosphorylation in mitochondria of transgenic mice. J Biol Chem 277:29626–29633

    Article  CAS  PubMed  Google Scholar 

  • Menzies FM, Ince PG, Shaw PJ (2002) Mitochondrial involvement in amyotrophic lateral sclerosis. Neurochem Int 40:543–551

    Article  CAS  PubMed  Google Scholar 

  • Miller RG, Rosenberg JA, Gelinas DF, Mitsumoto H, Newman D, Sufit R, Borasio GD, Bradley WG, Bromberg MB, Brooks BR, Kasarskis EJ, Munsat TL, Oppenheimer EA (1999) Practice parameter: the care of the patient with amyotrophic lateral sclerosis (an evidence-based review): report of the Quality Standards Subcommittee of the American Academy of Neurology: ALS Practice Parameters Task Force. Neurology 52:1311–1323

    Article  CAS  PubMed  Google Scholar 

  • Noh KM, Hwang JY, Shin HC, Koh JY (2000) A novel neuroprotective mechanism of riluzole: direct inhibition of protein kinase C. Neurobiol Dis 7:375–383

    Article  CAS  PubMed  Google Scholar 

  • Novalbos J, Abad-Santos F, Zapater P, Cano-Abad MF, Moradiellos J, Sanchez-Garcia P, Garcia AG (1999) Effects of dotarizine and flunarizine on chromaffin cell viability and cytosolic Ca2+. Eur J Pharmacol 366:309–317

    Article  CAS  PubMed  Google Scholar 

  • Ota M, Narahashi T, Keeler RF (1973) Effects of veratrum alkaloids on membrane potential and conductance of squid and crayfish giant axons. J Pharmacol Exp Ther 184:143–154

    CAS  PubMed  Google Scholar 

  • Pasinelli P, Brown RH (2006) Molecular biology of amyotrophic lateral sclerosis: insights from genetics. Nat Rev Neurosci 7:710–723

    Article  CAS  PubMed  Google Scholar 

  • Requejo R, Chouchani ET, James AM, Prime TA, Lilley KS, Fearnley IM, Murphy MP (2010) Quantification and identification of mitochondrial proteins containing vicinal dithiols. Arch Biochem Biophys 504:228–235

    Article  CAS  PubMed  Google Scholar 

  • Richter C, Gogvadze V, Laffranchi R, Schlapbach R, Schweizer M, Suter M, Walter P, Yaffee M (1995) Oxidants in mitochondria: from physiology to diseases. Biochim Biophys Acta 1271:67–74

    Article  PubMed  Google Scholar 

  • Rizzuto R, Pitton G, Azzone GF (1987) Effect of Ca2+, peroxides, SH reagents, phosphate and aging on the permeability of mitochondrial membranes. Eur J Biochem 162:239–249

    Article  CAS  PubMed  Google Scholar 

  • Ro LS, Lai SL, Chen CM, Chen ST (2003) Deleted 4977-bp mitochondrial DNA mutation is associated with sporadic amyotrophic lateral sclerosis: a hospital-based case-control study. Muscle Nerve 28:737–743

    Article  CAS  PubMed  Google Scholar 

  • Rosen DR (1993) Mutations in Cu/Zn superoxide dismutase gene are associated with familial amyotrophic lateral sclerosis. Nature 364:362

    CAS  PubMed  Google Scholar 

  • Rothstein JD, Tsai G, Kuncl RW, Clawson L, Cornblath DR, Drachman DB, Pestronk A, Stauch BL, Coyle JT (1990) Abnormal excitatory amino acid metabolism in amyotrophic lateral sclerosis. Ann Neurol 28:18–25

    Article  CAS  PubMed  Google Scholar 

  • Rothstein JD, Van Kammen M, Levey AI, Martin LJ, Kuncl RW (1995) Selective loss of glial glutamate transporter GLT-1 in amyotrophic lateral sclerosis. Ann Neurol 38:73–84

    Article  CAS  PubMed  Google Scholar 

  • Rowland LP, Shneider NA (2001) Amyotrophic lateral sclerosis. N Engl J Med 344:1688–1700

    Article  CAS  PubMed  Google Scholar 

  • Sasaki S, Iwata M (1996) Ultrastructural study of synapses in the anterior horn neurons of patients with amyotrophic lateral sclerosis. Neurosci Lett 204:53–56

    Article  CAS  PubMed  Google Scholar 

  • Sasaki S, Warita H, Komori T, Murakami T, Abe K, Iwata M (2006) Parvalbumin and calbindin D-28 k immunoreactivity in transgenic mice with a G93A mutant SOD1 gene. Brain Res 1083:196–203

    Article  CAS  PubMed  Google Scholar 

  • Schwaller B, Meyer M, Schiffmann S (2002) ‘New’ functions for ‘old’ proteins: the role of the calcium-binding proteins calbindin D-28k, calretinin and parvalbumin, in cerebellar physiology. Studies with knockout mice. Cerebellum 1:241–258

    Article  CAS  PubMed  Google Scholar 

  • Shaw PJ, Forrest V, Ince PG, Richardson JP, Wastell HJ (1995) CSF and plasma amino acid levels in motor neuron disease: elevation of CSF glutamate in a subset of patients. Neurodegeneration 4:209–216

    Article  CAS  PubMed  Google Scholar 

  • Siniscalchi A, Bonci A, Mercuri NB, Bernardi G (1997) Effects of riluzole on rat cortical neurones: an in vitro electrophysiological study. Br J Pharmacol 120:225–230

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Song JH, Huang CS, Nagata K, Yeh JZ, Narahashi T (1997) Differential action of riluzole on tetrodotoxin-sensitive and tetrodotoxin-resistant sodium channels. J Pharmacol Exp Ther 282:707–714

    CAS  PubMed  Google Scholar 

  • Van Den Bosch L, Vandenberghe W, Klaassen H, Van Houtte E, Robberecht W (2000) Ca(2+)-permeable AMPA receptors and selective vulnerability of motor neurons. J Neurol Sci 180:29–34

    Article  Google Scholar 

  • Van Den Bosch L, Van Damme P, Bogaert E, Robberecht W (2006) The role of excitotoxicity in the pathogenesis of amyotrophic lateral sclerosis. Biochim Biophys Acta 1762:1068–1082

    Article  Google Scholar 

  • Vielhaber S, Kunz D, Winkler K, Wiedemann FR, Kirches E, Feistner H, Heinze HJ, Elger CE, Schubert W, Kunz WS (2000) Mitochondrial DNA abnormalities in skeletal muscle of patients with sporadic amyotrophic lateral sclerosis. Brain 123(Pt 7):1339–1348

    Article  PubMed  Google Scholar 

  • von Lewinski F, Keller BU (2005) Ca2+, mitochondria and selective motoneuron vulnerability: implications for ALS. Trends Neurosci 28:494–500

    Article  Google Scholar 

  • Wang YJ, Lin MW, Lin AA, Wu SN (2008) Riluzole-induced block of voltage-gated Na+ current and activation of BKCa channels in cultured differentiated human skeletal muscle cells. Life Sci 82:11–20

    Article  CAS  PubMed  Google Scholar 

  • Wiedemann FR, Winkler K, Kuznetsov AV, Bartels C, Vielhaber S, Feistner H, Kunz WS (1998) Impairment of mitochondrial function in skeletal muscle of patients with amyotrophic lateral sclerosis. J Neurol Sci 156:65–72

    Article  CAS  PubMed  Google Scholar 

  • Wijesekera LC, Leigh PN (2009) Amyotrophic lateral sclerosis. Orphanet J Rare Dis 4:3

    Article  PubMed  PubMed Central  Google Scholar 

  • Yokoo H, Shiraishi S, Kobayashi H, Yanagita T, Yamamoto R, Wada A (1998) Selective inhibition by riluzole of voltage-dependent sodium channels and catecholamine secretion in adrenal chromaffin cells. Naunyn Schmiedebergs Arch Pharmacol 357:526–531

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank the Fundación Teófilo Hernando for continued support.

Funding

This study was partly supported by the following grants: “FIS” [nº PI052124] to ARN.“RENEVAS, IS Carlos III” [nº R006/00260009] and “MINECO” [nº SAF 2013-44108-T] to AGG, “Spanish Ministry of Science and Innovation” [nº BFU2007-64963], “La Caixa” [No. BN05-32-O] and “Groups’ Consolidation UAM-CAM” [nº 1004040047] to MFCA. “Ministry of Economy and Competitiveness/FPU Program” [nº AP2009/0343] to AJMO.

Author information

Authors and Affiliations

  1. Instituto Teófilo Hernando,Facultad de Medicina, Universidad Autónoma de Madrid, C/Arzobispo Morcillo, 4, 28029, Madrid, Spain

    Ana J. Moreno-Ortega, Lamiaa Mouhid Al-achbili, Elba Alonso, Cristóbal de los Ríos, Antonio G. García, Ana Ruiz-Nuño & María F. Cano-Abad

  2. Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, Madrid, Spain

    Ana J. Moreno-Ortega, Lamiaa Mouhid Al-achbili, Cristóbal de los Ríos, Antonio G. García & María F. Cano-Abad

  3. Servicio de Farmacología Clínica, Instituto de Investigación Sanitaria, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, C/Diego de León 62, 28006, Madrid, Spain

    Ana J. Moreno-Ortega, Elba Alonso, Antonio G. García, Ana Ruiz-Nuño & María F. Cano-Abad

Authors
  1. Ana J. Moreno-Ortega
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lamiaa Mouhid Al-achbili
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elba Alonso
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Cristóbal de los Ríos
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Antonio G. García
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Ana Ruiz-Nuño
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. María F. Cano-Abad
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Ana Ruiz-Nuño or María F. Cano-Abad.

Ethics declarations

Conflict of Interest

The authors declare that they have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary Fig. 1

Toxicity curves for ITH33/IQM9.21 (ITH33) and riluzole (Ril) per se in NSC-34 cells. Cell viability was measured after 24 h incubation with ITH33 (a) and Ril (b) at 1, 3, and 10 μM. Data are expressed as mean ± SEM of at least 18 experiments from at least 6 different cultures. Data are expressed as a percentage of the control (C). No statistically significant differences were presented in any case (1-way ANOVA, Bonferroni multiple comparison test) (PPT 152 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Moreno-Ortega, A.J., Al-achbili, L.M., Alonso, E. et al. Neuroprotective Effect of the Novel Compound ITH33/IQM9.21 Against Oxidative Stress and Na+ and Ca2+ Overload in Motor Neuron-like NSC-34 Cells. Neurotox Res 30, 380–391 (2016). https://doi.org/10.1007/s12640-016-9623-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12640-016-9623-7

Keywords

Search

Navigation