Tags

Type your tag names separated by a space and hit enter

Early modulation of the transcription factor Nrf2 in rodent striatal slices by quinolinic acid, a toxic metabolite of the kynurenine pathway.
Neuroscience. 2014 Feb 28; 260:130-9.N

Abstract

Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor involved in the orchestration of antioxidant responses. Although its pharmacological activation has been largely hypothesized as a promising tool to ameliorate the progression of neurodegenerative events, the actual knowledge about its modulation in neurotoxic paradigms remains scarce. In this study, we investigated the early profile of Nrf2 modulation in striatal slices of rodents incubated in the presence of the toxic kynurenine pathway metabolite, quinolinic acid (QUIN). Tissue slices from rats and mice were obtained and used throughout the experiments in order to compare inter-species responses. Nuclear Nrf2 protein levels and oxidative damage to lipids were compared. Time- and concentration-response curves of all markers were explored. Nrf2 nuclear activation was corroborated through phase 2 antioxidant protein expression. The effects of QUIN on Nrf2 modulation and oxidative stress were also compared between slices of wild-type (Nrf2(+/+)) and Nrf2 knock-out (Nrf2(-/-)) mice. The possible involvement of the N-methyl-d-aspartate receptor (NMDAr) in the Nrf2 modulation and lipid peroxidation was further explored in mice striatal slices. In rat striatal slices, QUIN stimulated the Nrf2 nuclear translocation. This effect was accompanied by augmented lipid peroxidation. In the mouse striatum, QUIN per se exerted an induction of Nrf2 factor only at 1h of incubation, and a concentration-response effect on lipid peroxidation after 3h of incubation. QUIN stimulated the striatal content of phase 2 enzymes. Nrf2(-/-) mice were slightly more responsive than Nrf2(+/+) mice to the QUIN-induced oxidative damage, and completely unresponsive to the NMDAr antagonist MK-801 when tested against QUIN. Findings of this study indicate that: (1) Nrf2 is modulated in rodent striatal tissue in response to QUIN; (2) Nrf2(-/-) striatal tissue was moderately more vulnerable to oxidative damage than the Wt condition; and (3) early Nrf2 up-regulation reflects a compensatory response to the QUIN-induced oxidative stress in course as part of a general defense system, whereas Nrf2 down-regulation might contribute to more intense oxidative cell damage.

Authors+Show Affiliations

Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, S.S.A., Mexico City, Mexico.Instituto Nacional de Geriatría, S.S.A., Mexico City, Mexico.Departamento de Ciencias de la Salud, DCBS, Universidad Autónoma Metropolitana Iztapalapa, Mexico City, Mexico.Division of Neurotoxicology, National Center for Toxicological Research, FDA, Jefferson, AR, USA.Departamento de Biología, Facultad de Química, Universidad Nacional Autónoma de México, Mexico City, Mexico.Laboratorio de Aminoácidos Excitadores, Instituto Nacional de Neurología y Neurocirugía, S.S.A., Mexico City, Mexico. Electronic address: absada@yahoo.com.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24361737

Citation

Colín-González, A L., et al. "Early Modulation of the Transcription Factor Nrf2 in Rodent Striatal Slices By Quinolinic Acid, a Toxic Metabolite of the Kynurenine Pathway." Neuroscience, vol. 260, 2014, pp. 130-9.
Colín-González AL, Luna-López A, Königsberg M, et al. Early modulation of the transcription factor Nrf2 in rodent striatal slices by quinolinic acid, a toxic metabolite of the kynurenine pathway. Neuroscience. 2014;260:130-9.
Colín-González, A. L., Luna-López, A., Königsberg, M., Ali, S. F., Pedraza-Chaverrí, J., & Santamaría, A. (2014). Early modulation of the transcription factor Nrf2 in rodent striatal slices by quinolinic acid, a toxic metabolite of the kynurenine pathway. Neuroscience, 260, 130-9. https://doi.org/10.1016/j.neuroscience.2013.12.025
Colín-González AL, et al. Early Modulation of the Transcription Factor Nrf2 in Rodent Striatal Slices By Quinolinic Acid, a Toxic Metabolite of the Kynurenine Pathway. Neuroscience. 2014 Feb 28;260:130-9. PubMed PMID: 24361737.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Early modulation of the transcription factor Nrf2 in rodent striatal slices by quinolinic acid, a toxic metabolite of the kynurenine pathway. AU - Colín-González,A L, AU - Luna-López,A, AU - Königsberg,M, AU - Ali,S F, AU - Pedraza-Chaverrí,J, AU - Santamaría,A, Y1 - 2013/12/19/ PY - 2013/08/30/received PY - 2013/12/09/revised PY - 2013/12/11/accepted PY - 2013/12/24/entrez PY - 2013/12/24/pubmed PY - 2014/9/26/medline KW - ARE KW - DMF KW - EDTA KW - EGTA KW - HD KW - HEPES KW - HO-1 KW - Huntington’s disease KW - KP KW - Kynurenine pathway KW - MDA KW - MK-801 KW - N-methyl-d-aspartate receptor KW - NAD(P)H KW - NMDAr KW - Nrf2 KW - Nuclear factor (erythroid-derived 2)-like 2 KW - QUIN KW - ROS KW - S-allyl cysteine KW - SAC KW - SOD KW - TBARS KW - antioxidant defense KW - antioxidant response element KW - dimethylfumarate KW - dizocilpine KW - ethylene glycol tetraacetic acid KW - ethylenediaminetetraacetic acid KW - excitotoxicity KW - gamma-glutamylcysteine ligase-C KW - heme oxygenase-1 KW - hydroxyethyl piperazineethanesulfonic acid KW - kynurenine pathway KW - malondialdehyde KW - nicotinamide adenine dinucleotide phosphate-oxidase KW - oxidative stress KW - quinolinic acid KW - reactive oxygen species KW - superoxide dismutase KW - tBHQ KW - tert-butylhydroquinone KW - thiobarbituric acid reactive substances KW - γ-GCL-C SP - 130 EP - 9 JF - Neuroscience JO - Neuroscience VL - 260 N2 - Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is a transcription factor involved in the orchestration of antioxidant responses. Although its pharmacological activation has been largely hypothesized as a promising tool to ameliorate the progression of neurodegenerative events, the actual knowledge about its modulation in neurotoxic paradigms remains scarce. In this study, we investigated the early profile of Nrf2 modulation in striatal slices of rodents incubated in the presence of the toxic kynurenine pathway metabolite, quinolinic acid (QUIN). Tissue slices from rats and mice were obtained and used throughout the experiments in order to compare inter-species responses. Nuclear Nrf2 protein levels and oxidative damage to lipids were compared. Time- and concentration-response curves of all markers were explored. Nrf2 nuclear activation was corroborated through phase 2 antioxidant protein expression. The effects of QUIN on Nrf2 modulation and oxidative stress were also compared between slices of wild-type (Nrf2(+/+)) and Nrf2 knock-out (Nrf2(-/-)) mice. The possible involvement of the N-methyl-d-aspartate receptor (NMDAr) in the Nrf2 modulation and lipid peroxidation was further explored in mice striatal slices. In rat striatal slices, QUIN stimulated the Nrf2 nuclear translocation. This effect was accompanied by augmented lipid peroxidation. In the mouse striatum, QUIN per se exerted an induction of Nrf2 factor only at 1h of incubation, and a concentration-response effect on lipid peroxidation after 3h of incubation. QUIN stimulated the striatal content of phase 2 enzymes. Nrf2(-/-) mice were slightly more responsive than Nrf2(+/+) mice to the QUIN-induced oxidative damage, and completely unresponsive to the NMDAr antagonist MK-801 when tested against QUIN. Findings of this study indicate that: (1) Nrf2 is modulated in rodent striatal tissue in response to QUIN; (2) Nrf2(-/-) striatal tissue was moderately more vulnerable to oxidative damage than the Wt condition; and (3) early Nrf2 up-regulation reflects a compensatory response to the QUIN-induced oxidative stress in course as part of a general defense system, whereas Nrf2 down-regulation might contribute to more intense oxidative cell damage. SN - 1873-7544 UR - https://www.unboundmedicine.com/medline/citation/24361737/Early_modulation_of_the_transcription_factor_Nrf2_in_rodent_striatal_slices_by_quinolinic_acid_a_toxic_metabolite_of_the_kynurenine_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0306-4522(13)01041-5 DB - PRIME DP - Unbound Medicine ER -