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In vivo induction of heat shock proteins in the substantia nigra following L-DOPA administration is associated with increased activity of mitochondrial complex I and nitrosative stress in rats: regulation by glutathione redox state.
J Neurochem. 2007 May; 101(3):709-17.JN

Abstract

Increasing evidence suggests a critical role for oxidative and nitrosative stress in the pathogenesis of most important neurodegenerative disorders. Parkinson's disease (PD) is a neurodegenerative disease characterized by a severe depletion in number of dopaminergic cells of the substantia nigra (SN). Administration of L-DOPA (LD) is the more effective treatment for patients with PD. However, the vast majority of patients suffer LD-related complications, which represent the major problem in the clinical management of PD. In the present study, LD administration to rats resulted in a significant dose-dependent increase in Hsp70 synthesis which was specific for the SN. The amount of 70 kDa protein increased after 6 h treatment reaching the maximal induction after 24-48 h. Induction of Hsp70 in the SN was associated with a significant increase in constitutive Hsc70 and mitochondrial Hsp60 stress proteins, and with increased expression of mitochondrial complex I whereas no significant changes were found in the activity of complex IV. In the same experimental conditions, a significant decrease in reduced glutathione was observed, which was associated with an increased content of oxidized glutathione content as well as nitric oxide (NO) synthase activity, NO metabolites and nitrotyrosine immunoreactivity. Interestingly, Hsp70 induction, iNOS up-regulation and nitrotyrosine formation have been confirmed also in SN and striatum of rats treated with LD and carbidopa, this latter being an inhibitor of the peripheral DOPA decarboxylase. Our data are in favor of the importance of the heat shock signal pathway as a basic mechanism of defense against neurotoxicity elicited by free radical oxygen and nitrogen species produced in aging and neurodegenerative disorders.

Authors+Show Affiliations

Department of Chemistry, Biochemistry and Molecular Biology Section, Faculty of Medicine, University of Catania, Catania, Italy. calabres@mbox.unict.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17241115

Citation

Calabrese, Vittorio, et al. "In Vivo Induction of Heat Shock Proteins in the Substantia Nigra Following L-DOPA Administration Is Associated With Increased Activity of Mitochondrial Complex I and Nitrosative Stress in Rats: Regulation By Glutathione Redox State." Journal of Neurochemistry, vol. 101, no. 3, 2007, pp. 709-17.
Calabrese V, Mancuso C, Ravagna A, et al. In vivo induction of heat shock proteins in the substantia nigra following L-DOPA administration is associated with increased activity of mitochondrial complex I and nitrosative stress in rats: regulation by glutathione redox state. J Neurochem. 2007;101(3):709-17.
Calabrese, V., Mancuso, C., Ravagna, A., Perluigi, M., Cini, C., De Marco, C., Butterfield, D. A., & Stella, A. M. (2007). In vivo induction of heat shock proteins in the substantia nigra following L-DOPA administration is associated with increased activity of mitochondrial complex I and nitrosative stress in rats: regulation by glutathione redox state. Journal of Neurochemistry, 101(3), 709-17.
Calabrese V, et al. In Vivo Induction of Heat Shock Proteins in the Substantia Nigra Following L-DOPA Administration Is Associated With Increased Activity of Mitochondrial Complex I and Nitrosative Stress in Rats: Regulation By Glutathione Redox State. J Neurochem. 2007;101(3):709-17. PubMed PMID: 17241115.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vivo induction of heat shock proteins in the substantia nigra following L-DOPA administration is associated with increased activity of mitochondrial complex I and nitrosative stress in rats: regulation by glutathione redox state. AU - Calabrese,Vittorio, AU - Mancuso,Cesare, AU - Ravagna,Agrippino, AU - Perluigi,Marzia, AU - Cini,Chiara, AU - De Marco,Carlo, AU - Butterfield,D Allan, AU - Stella,Anna Maria Giuffrida, Y1 - 2007/01/04/ PY - 2007/1/24/pubmed PY - 2007/7/19/medline PY - 2007/1/24/entrez SP - 709 EP - 17 JF - Journal of neurochemistry JO - J Neurochem VL - 101 IS - 3 N2 - Increasing evidence suggests a critical role for oxidative and nitrosative stress in the pathogenesis of most important neurodegenerative disorders. Parkinson's disease (PD) is a neurodegenerative disease characterized by a severe depletion in number of dopaminergic cells of the substantia nigra (SN). Administration of L-DOPA (LD) is the more effective treatment for patients with PD. However, the vast majority of patients suffer LD-related complications, which represent the major problem in the clinical management of PD. In the present study, LD administration to rats resulted in a significant dose-dependent increase in Hsp70 synthesis which was specific for the SN. The amount of 70 kDa protein increased after 6 h treatment reaching the maximal induction after 24-48 h. Induction of Hsp70 in the SN was associated with a significant increase in constitutive Hsc70 and mitochondrial Hsp60 stress proteins, and with increased expression of mitochondrial complex I whereas no significant changes were found in the activity of complex IV. In the same experimental conditions, a significant decrease in reduced glutathione was observed, which was associated with an increased content of oxidized glutathione content as well as nitric oxide (NO) synthase activity, NO metabolites and nitrotyrosine immunoreactivity. Interestingly, Hsp70 induction, iNOS up-regulation and nitrotyrosine formation have been confirmed also in SN and striatum of rats treated with LD and carbidopa, this latter being an inhibitor of the peripheral DOPA decarboxylase. Our data are in favor of the importance of the heat shock signal pathway as a basic mechanism of defense against neurotoxicity elicited by free radical oxygen and nitrogen species produced in aging and neurodegenerative disorders. SN - 0022-3042 UR - https://www.unboundmedicine.com/medline/citation/17241115/In_vivo_induction_of_heat_shock_proteins_in_the_substantia_nigra_following_L_DOPA_administration_is_associated_with_increased_activity_of_mitochondrial_complex_I_and_nitrosative_stress_in_rats:_regulation_by_glutathione_redox_state_ L2 - https://doi.org/10.1111/j.1471-4159.2006.04367.x DB - PRIME DP - Unbound Medicine ER -