Tags

Type your tag names separated by a space and hit enter

Novel imine antioxidants at low nanomolar concentrations protect dopaminergic cells from oxidative neurotoxicity.
J Neurochem. 2009 Jul; 110(1):118-32.JN

Abstract

Strong evidence indicates that oxidative stress may be causally involved in the pathogenesis of Parkinson's disease. We have employed human dopaminergic neuroblastoma cells and rat primary mesencephalic neurons to assess the protective potential of three novel bisarylimine antioxidants on dopaminergic cell death induced by complex I inhibition or glutathione depletion. We have found that exceptionally low concentrations (EC(50) values approximately 20 nM) of these compounds (iminostilbene, phenothiazine, and phenoxazine) exhibited strong protective effects against the toxicities of MPP(+), rotenone, and l-buthionine sulfoximine. Investigating intracellular glutathione levels, it was found that MPP(+), L-buthionine sulfoximine, and rotenone disrupted different aspects of the native glutathione equilibrium, while the aromatic imines did not further influence glutathione levels or redox state on any baseline. However, the imines independently reduced protein oxidation and total oxidant flux, saved the mitochondrial membrane potential, and provided full cytoprotection under conditions of complete glutathione depletion. The unusually potent antioxidant effects of the bisarylimines could be reproduced in isolated mitochondria, which were instantly protected from lipid peroxidation and pathological swelling. Aromatic imines may be interesting lead structures for a potential antioxidant therapy of Parkinson's disease and other disorders accompanied by glutathione dysregulation.

Authors+Show Affiliations

Department of Pathobiochemistry, University Medical Center of the Johannes Gutenberg University, Mainz, Germany.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19486265

Citation

Hajieva, Parvana, et al. "Novel Imine Antioxidants at Low Nanomolar Concentrations Protect Dopaminergic Cells From Oxidative Neurotoxicity." Journal of Neurochemistry, vol. 110, no. 1, 2009, pp. 118-32.
Hajieva P, Mocko JB, Moosmann B, et al. Novel imine antioxidants at low nanomolar concentrations protect dopaminergic cells from oxidative neurotoxicity. J Neurochem. 2009;110(1):118-32.
Hajieva, P., Mocko, J. B., Moosmann, B., & Behl, C. (2009). Novel imine antioxidants at low nanomolar concentrations protect dopaminergic cells from oxidative neurotoxicity. Journal of Neurochemistry, 110(1), 118-32. https://doi.org/10.1111/j.1471-4159.2009.06114.x
Hajieva P, et al. Novel Imine Antioxidants at Low Nanomolar Concentrations Protect Dopaminergic Cells From Oxidative Neurotoxicity. J Neurochem. 2009;110(1):118-32. PubMed PMID: 19486265.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Novel imine antioxidants at low nanomolar concentrations protect dopaminergic cells from oxidative neurotoxicity. AU - Hajieva,Parvana, AU - Mocko,Justyna B, AU - Moosmann,Bernd, AU - Behl,Christian, Y1 - 2009/05/26/ PY - 2009/6/3/entrez PY - 2009/6/3/pubmed PY - 2009/8/22/medline SP - 118 EP - 32 JF - Journal of neurochemistry JO - J Neurochem VL - 110 IS - 1 N2 - Strong evidence indicates that oxidative stress may be causally involved in the pathogenesis of Parkinson's disease. We have employed human dopaminergic neuroblastoma cells and rat primary mesencephalic neurons to assess the protective potential of three novel bisarylimine antioxidants on dopaminergic cell death induced by complex I inhibition or glutathione depletion. We have found that exceptionally low concentrations (EC(50) values approximately 20 nM) of these compounds (iminostilbene, phenothiazine, and phenoxazine) exhibited strong protective effects against the toxicities of MPP(+), rotenone, and l-buthionine sulfoximine. Investigating intracellular glutathione levels, it was found that MPP(+), L-buthionine sulfoximine, and rotenone disrupted different aspects of the native glutathione equilibrium, while the aromatic imines did not further influence glutathione levels or redox state on any baseline. However, the imines independently reduced protein oxidation and total oxidant flux, saved the mitochondrial membrane potential, and provided full cytoprotection under conditions of complete glutathione depletion. The unusually potent antioxidant effects of the bisarylimines could be reproduced in isolated mitochondria, which were instantly protected from lipid peroxidation and pathological swelling. Aromatic imines may be interesting lead structures for a potential antioxidant therapy of Parkinson's disease and other disorders accompanied by glutathione dysregulation. SN - 1471-4159 UR - https://www.unboundmedicine.com/medline/citation/19486265/Novel_imine_antioxidants_at_low_nanomolar_concentrations_protect_dopaminergic_cells_from_oxidative_neurotoxicity_ L2 - https://doi.org/10.1111/j.1471-4159.2009.06114.x DB - PRIME DP - Unbound Medicine ER -