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Published in: Inflammation Research 10/2018

01-10-2018 | Original Research Paper

Evaluation of neuroprotective effects of insulin on immuno-inflammatory and systemic disorders induced by kaliotoxin, a Kv1.3 channel blocker

Authors: Zahida Taibi-Djennah, Marie-France Martin-Eauclaire, Fatima Laraba-Djebari

Published in: Inflammation Research | Issue 10/2018

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Abstract

Objective

Kaliotoxin2 (KTX2) is a highly selective blocker of voltage-dependent potassium channels Kv1.3 containing 37 amino acid residues. It is purified from Androctonus australis scorpion venom. The binding of KTX2 to its targets is able to alter the neuronal excitability leading to neurological disorders, accompanied by an inflammatory response. In brain, activation of insulin receptor signaling pathway by insulin induces current suppression and concomitant tyrosine phosphorylation of Kv1.3 channel. The aim of this study is to evaluate the effect of insulin injected by i.c.v. route on the neuro-pathophysiological and systemic disorders induced by KTX2.

Materials and methods

Tissue damage, inflammatory response and oxidative stress biomarkers were assessed in NMRI mice at 24 h after co-injection of KTX2 and insulin by intracerebroventricular route.

Results

Obtained results revealed that the central administration of insulin prevents cerebral cortex injury, brain edema and blood–brain barrier alteration induced by KTX2, these are accompanied by significant decrease of systemic disorders including serum cytokines, inflammatory and oxidative stress markers and tissue damage.

Conclusion

These results indicate that insulin is able to reduce neuro-immunological effects and systemic disorders induced by KTX2. The neuroprotective effect of insulin may be due to its crucial role in the regulation of inflammation response and its properties to modulate the activity of Kv1.3 channels in brain.
Literature
2.
go back to reference Tytgat J, Chandy KG, Garcia ML, Gutman GA, Martin-Eauclaire MF, van der Walt JJ, et al. A unified nomenclature for short-chain peptides isolated from scorpion venoms: alpha-KTx molecular subfamilies. Trends Pharmacol. Sci. 1999;20(11):444–7.CrossRefPubMed Tytgat J, Chandy KG, Garcia ML, Gutman GA, Martin-Eauclaire MF, van der Walt JJ, et al. A unified nomenclature for short-chain peptides isolated from scorpion venoms: alpha-KTx molecular subfamilies. Trends Pharmacol. Sci. 1999;20(11):444–7.CrossRefPubMed
6.
go back to reference Laraba-Djebari F, Legros C, Crest M, Ceard B, Romi R, Mansuelle P, et al. The kaliotoxin family enlarged. Purification, characterization, and precursor nucleotide sequence of KTX2 from Androctonus australis venom. J Biol Chem. 1994;269(52):32835–43.PubMed Laraba-Djebari F, Legros C, Crest M, Ceard B, Romi R, Mansuelle P, et al. The kaliotoxin family enlarged. Purification, characterization, and precursor nucleotide sequence of KTX2 from Androctonus australis venom. J Biol Chem. 1994;269(52):32835–43.PubMed
12.
go back to reference Mourre C, Chernova MN, Martin-Eauclaire MF, Bessone R, Jacquet G, Gola M, et al. Distribution in rat brain of binding sites of kaliotoxin, a blocker of Kv1.1 and Kv1.3 alpha-subunits. J. Pharmacol. Exp. Ther. 1999;291(3):943–52.PubMed Mourre C, Chernova MN, Martin-Eauclaire MF, Bessone R, Jacquet G, Gola M, et al. Distribution in rat brain of binding sites of kaliotoxin, a blocker of Kv1.1 and Kv1.3 alpha-subunits. J. Pharmacol. Exp. Ther. 1999;291(3):943–52.PubMed
14.
go back to reference Lu J, Goh SJ, Tng PY, Deng YY, Ling EA, Moochhala S. Systemic inflammatory response following acute traumatic brain injury. Front Biosci (Landmark Ed). 2009;14:3795–813.CrossRef Lu J, Goh SJ, Tng PY, Deng YY, Ling EA, Moochhala S. Systemic inflammatory response following acute traumatic brain injury. Front Biosci (Landmark Ed). 2009;14:3795–813.CrossRef
16.
go back to reference Havrankova J, Roth J, Brownstein M. Insulin receptors are widely distributed in the central nervous system of the rat. Nature. 1978;272(5656):827–9.CrossRefPubMed Havrankova J, Roth J, Brownstein M. Insulin receptors are widely distributed in the central nervous system of the rat. Nature. 1978;272(5656):827–9.CrossRefPubMed
17.
go back to reference Fadool DA, Tucker K, Phillips JJ, Simmen JA. Brain insulin receptor causes activity-dependent current suppression in the olfactory bulb through multiple phosphorylation of Kv1.3. J. Neurophysiol. 2000;83(4):2332–48.CrossRefPubMedPubMedCentral Fadool DA, Tucker K, Phillips JJ, Simmen JA. Brain insulin receptor causes activity-dependent current suppression in the olfactory bulb through multiple phosphorylation of Kv1.3. J. Neurophysiol. 2000;83(4):2332–48.CrossRefPubMedPubMedCentral
19.
go back to reference Franklin JL, Bennett WL, Messina JL. Insulin attenuates TNFα-induced hemopexin mRNA: an anti-inflammatory action of insulin in rat H4IIE hepatoma cells. Biochem. Biophys. Rep. 2017;9:211–216PubMedPubMedCentral Franklin JL, Bennett WL, Messina JL. Insulin attenuates TNFα-induced hemopexin mRNA: an anti-inflammatory action of insulin in rat H4IIE hepatoma cells. Biochem. Biophys. Rep. 2017;9:211–216PubMedPubMedCentral
20.
go back to reference Andreelli F, Jacquier D, Keufer F. Propriétés anti-inflammatoires de l’insuline chez les patients en réanimation. Réanimation. 2006;15(6):467–73.CrossRef Andreelli F, Jacquier D, Keufer F. Propriétés anti-inflammatoires de l’insuline chez les patients en réanimation. Réanimation. 2006;15(6):467–73.CrossRef
21.
go back to reference Devos P. Effets propres de l’insuline par rapport au contrôle glycémique. Réanimation. 2008;17:8–11.CrossRef Devos P. Effets propres de l’insuline par rapport au contrôle glycémique. Réanimation. 2008;17:8–11.CrossRef
26.
go back to reference Matos IM, Souza DG, Seabra DG, Freire-Maia L, Teixeira MM. Effects of tachykinin NK1 or PAF receptor blockade on the lung injury induced by scorpion venom in rats. Eur. J. Pharmacol. 1999;376(3):293–300.CrossRefPubMed Matos IM, Souza DG, Seabra DG, Freire-Maia L, Teixeira MM. Effects of tachykinin NK1 or PAF receptor blockade on the lung injury induced by scorpion venom in rats. Eur. J. Pharmacol. 1999;376(3):293–300.CrossRefPubMed
27.
go back to reference Somiari SB, Somiari RI, Heckman CM, Olsen CH, Jordan RM, Russell SJ, et al. Circulating MMP2 and MMP9 in breast cancer—potential role in classification of patients into low risk, high risk, benign disease and breast cancer categories. Int. J. Cancer. 2006;119(6):1403–11. https://doi.org/10.1002/ijc.21989.CrossRefPubMed Somiari SB, Somiari RI, Heckman CM, Olsen CH, Jordan RM, Russell SJ, et al. Circulating MMP2 and MMP9 in breast cancer—potential role in classification of patients into low risk, high risk, benign disease and breast cancer categories. Int. J. Cancer. 2006;119(6):1403–11. https://​doi.​org/​10.​1002/​ijc.​21989.CrossRefPubMed
30.
go back to reference Van Oosterhout AJ, van Ark I, Hofman G, Van Der Linde HJ, Fattah D, Nijkamp FP. Role of interleukin-5 and substance P in development of airway hyperreactivity to histamine in guinea-pigs. Eur. Respir. J. 1996;9(3):493–9.CrossRefPubMed Van Oosterhout AJ, van Ark I, Hofman G, Van Der Linde HJ, Fattah D, Nijkamp FP. Role of interleukin-5 and substance P in development of airway hyperreactivity to histamine in guinea-pigs. Eur. Respir. J. 1996;9(3):493–9.CrossRefPubMed
31.
go back to reference Sun XC, Li WB, Li SQ, Li QJ, Chen XL, Ai J. Intrathecal injection of Sar9, Met(O2)11-substance P, neurokinin-1 receptor agonist, increases nitric oxide synthase expression and nitric oxide production in the rat spinal cord. Acta Physiol. Sin. 2003;55(6):677–83. Sun XC, Li WB, Li SQ, Li QJ, Chen XL, Ai J. Intrathecal injection of Sar9, Met(O2)11-substance P, neurokinin-1 receptor agonist, increases nitric oxide synthase expression and nitric oxide production in the rat spinal cord. Acta Physiol. Sin. 2003;55(6):677–83.
33.
go back to reference Sampaio SC, Sousa-e-Silva MC, Borelli P, Curi R, Cury Y. Crotalus durissus terrificus snake venom regulates macrophage metabolism and function. J. Leukoc. Biol. 2001;70(4):551–8.PubMed Sampaio SC, Sousa-e-Silva MC, Borelli P, Curi R, Cury Y. Crotalus durissus terrificus snake venom regulates macrophage metabolism and function. J. Leukoc. Biol. 2001;70(4):551–8.PubMed
36.
go back to reference Dardiotis E, Karanikas V, Paterakis K, Fountas K, Hadjigeorgiou GM. Traumatic brain injury and inflammation: emerging role of innate and adaptive immunity. In: Agrawal A, editor. Brain injury-pathogenesis, monitoring, recovery and management. Rijeka: InTech; 2012. p. 23–38. Dardiotis E, Karanikas V, Paterakis K, Fountas K, Hadjigeorgiou GM. Traumatic brain injury and inflammation: emerging role of innate and adaptive immunity. In: Agrawal A, editor. Brain injury-pathogenesis, monitoring, recovery and management. Rijeka: InTech; 2012. p. 23–38.
40.
go back to reference de Vries HE, Kuiper J, de Boer AG, Van Berkel TJ, Breimer DD. The blood–brain barrier in neuroinflammatory diseases. Pharmacol. Rev. 1997;49(2):143–55.PubMed de Vries HE, Kuiper J, de Boer AG, Van Berkel TJ, Breimer DD. The blood–brain barrier in neuroinflammatory diseases. Pharmacol. Rev. 1997;49(2):143–55.PubMed
43.
go back to reference Kossakowska AE, Edwards DR, Prusinkiewicz C, Zhang MC, Guo D, Urbanski SJ, et al. Interleukin-6 regulation of matrix metalloproteinase (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) expression in malignant non-Hodgkin’s lymphomas. Blood. 1999;94(6):2080–9.PubMed Kossakowska AE, Edwards DR, Prusinkiewicz C, Zhang MC, Guo D, Urbanski SJ, et al. Interleukin-6 regulation of matrix metalloproteinase (MMP-2 and MMP-9) and tissue inhibitor of metalloproteinase (TIMP-1) expression in malignant non-Hodgkin’s lymphomas. Blood. 1999;94(6):2080–9.PubMed
44.
45.
47.
go back to reference Koffler M, Raskin P, Womble D, Helderman JH. Immunobiological consequence of regulation of insulin receptor on alloactivated lymphocytes in normal and obese subjects. Diabetes. 1991;40(3):364–70.CrossRefPubMed Koffler M, Raskin P, Womble D, Helderman JH. Immunobiological consequence of regulation of insulin receptor on alloactivated lymphocytes in normal and obese subjects. Diabetes. 1991;40(3):364–70.CrossRefPubMed
51.
go back to reference Klein D, Schubert T, Horch RE, Jauch KW, Jeschke MG. Insulin treatment improves hepatic morphology and function through modulation of hepatic signals after severe trauma. Ann. Surg. 2004;240(2):340–9.CrossRefPubMedPubMedCentral Klein D, Schubert T, Horch RE, Jauch KW, Jeschke MG. Insulin treatment improves hepatic morphology and function through modulation of hepatic signals after severe trauma. Ann. Surg. 2004;240(2):340–9.CrossRefPubMedPubMedCentral
55.
go back to reference Bailey SL, Carpentier PA, McMahon EJ, Begolka WS, Miller SD. Innate and adaptive immune responses of the central nervous system. Crit. Rev. Immunol. 2006;26(2):149–88.CrossRefPubMed Bailey SL, Carpentier PA, McMahon EJ, Begolka WS, Miller SD. Innate and adaptive immune responses of the central nervous system. Crit. Rev. Immunol. 2006;26(2):149–88.CrossRefPubMed
56.
go back to reference Imhof BA, Engelhardt B, Vadas M. Novel mechanisms of the transendothelial migration of leukocytes. Trends Immunol. 2001;22(8):411–4.CrossRefPubMed Imhof BA, Engelhardt B, Vadas M. Novel mechanisms of the transendothelial migration of leukocytes. Trends Immunol. 2001;22(8):411–4.CrossRefPubMed
63.
69.
go back to reference Fatani AJ, Furman BL, Zeitlin IJ. The involvement of plasma kinins in the cardiovascular effects of Leiurus quinquestriatus scorpion venom in anaesthetised rabbits. Toxicon. 1998;36(3):523–36.CrossRefPubMed Fatani AJ, Furman BL, Zeitlin IJ. The involvement of plasma kinins in the cardiovascular effects of Leiurus quinquestriatus scorpion venom in anaesthetised rabbits. Toxicon. 1998;36(3):523–36.CrossRefPubMed
Metadata
Title
Evaluation of neuroprotective effects of insulin on immuno-inflammatory and systemic disorders induced by kaliotoxin, a Kv1.3 channel blocker
Authors
Zahida Taibi-Djennah
Marie-France Martin-Eauclaire
Fatima Laraba-Djebari
Publication date
01-10-2018
Publisher
Springer International Publishing
Published in
Inflammation Research / Issue 10/2018
Print ISSN: 1023-3830
Electronic ISSN: 1420-908X
DOI
https://doi.org/10.1007/s00011-018-1177-0

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