Tags

Type your tag names separated by a space and hit enter

3-nitropropionic acid-induced mitochondrial permeability transition: comparative study of mitochondria from different tissues and brain regions.
J Neurosci Res. 2010 Feb 15; 88(3):630-9.JN

Abstract

The adult rat striatum is particularly vulnerable to systemic administration of the succinate dehydrogenase inhibitor 3-nitropropionic acid (3NP), which is known to induce degeneration of the caudate-putamen, as occurs in Huntington's disease. The aim of the present study was to compare the susceptibility of isolated mitochondria from different rat brain regions (striatum, cortex, and cerebellum) as well as from the liver, kidney, and heart to mitochondrial permeability transition (MPT) induced by 3NP and Ca(2+). In the presence of micromolar Ca(2+) concentrations, 3NP induces MPT in a dose-dependent manner, as estimated by mitochondrial swelling and a decrease in the transmembrane electrical potential. A 3NP concentration capable of promoting a 10% inhibition of ADP-stimulated, succinate-supported respiration was sufficient to stimulate Ca(2+)-induced MPT. Brain and heart mitochondria were generally more sensitive to 3NP and Ca(2+)-induced MPT than mitochondria from liver and kidney. In addition, a partial inhibition of mitochondrial respiration by 3NP resulted in more pronounced MPT in striatal mitochondria than in cortical or cerebellar organelles. A similar inhibition of succinate dehydrogenase activity was observed in rat tissue homogenates obtained from various brain regions as well as from liver, kidney, and heart 24 hr after a single i.p. 3NP dose. Mitochondria isolated from forebrains of 3NP-treated rats were also more susceptible to Ca(2+)-induced MPT than those of control rats. We propose that the increased susceptibility of the striatum to 3NP-induced neurodegeneration may be partially explained by its susceptibility to MPT, together with the greater vulnerability of this brain region to glutamate receptor-mediated Ca(2+) influx.

Authors+Show Affiliations

Departamento de Patologia Clínica, Faculdade de Ciências Médicas, Universidade Estadual de Campinas , Campinas, Brazil.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

19795369

Citation

Mirandola, Sandra R., et al. "3-nitropropionic Acid-induced Mitochondrial Permeability Transition: Comparative Study of Mitochondria From Different Tissues and Brain Regions." Journal of Neuroscience Research, vol. 88, no. 3, 2010, pp. 630-9.
Mirandola SR, Melo DR, Saito A, et al. 3-nitropropionic acid-induced mitochondrial permeability transition: comparative study of mitochondria from different tissues and brain regions. J Neurosci Res. 2010;88(3):630-9.
Mirandola, S. R., Melo, D. R., Saito, A., & Castilho, R. F. (2010). 3-nitropropionic acid-induced mitochondrial permeability transition: comparative study of mitochondria from different tissues and brain regions. Journal of Neuroscience Research, 88(3), 630-9. https://doi.org/10.1002/jnr.22239
Mirandola SR, et al. 3-nitropropionic Acid-induced Mitochondrial Permeability Transition: Comparative Study of Mitochondria From Different Tissues and Brain Regions. J Neurosci Res. 2010 Feb 15;88(3):630-9. PubMed PMID: 19795369.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 3-nitropropionic acid-induced mitochondrial permeability transition: comparative study of mitochondria from different tissues and brain regions. AU - Mirandola,Sandra R, AU - Melo,Daniela R, AU - Saito,Angela, AU - Castilho,Roger F, PY - 2009/10/2/entrez PY - 2009/10/2/pubmed PY - 2010/3/31/medline SP - 630 EP - 9 JF - Journal of neuroscience research JO - J Neurosci Res VL - 88 IS - 3 N2 - The adult rat striatum is particularly vulnerable to systemic administration of the succinate dehydrogenase inhibitor 3-nitropropionic acid (3NP), which is known to induce degeneration of the caudate-putamen, as occurs in Huntington's disease. The aim of the present study was to compare the susceptibility of isolated mitochondria from different rat brain regions (striatum, cortex, and cerebellum) as well as from the liver, kidney, and heart to mitochondrial permeability transition (MPT) induced by 3NP and Ca(2+). In the presence of micromolar Ca(2+) concentrations, 3NP induces MPT in a dose-dependent manner, as estimated by mitochondrial swelling and a decrease in the transmembrane electrical potential. A 3NP concentration capable of promoting a 10% inhibition of ADP-stimulated, succinate-supported respiration was sufficient to stimulate Ca(2+)-induced MPT. Brain and heart mitochondria were generally more sensitive to 3NP and Ca(2+)-induced MPT than mitochondria from liver and kidney. In addition, a partial inhibition of mitochondrial respiration by 3NP resulted in more pronounced MPT in striatal mitochondria than in cortical or cerebellar organelles. A similar inhibition of succinate dehydrogenase activity was observed in rat tissue homogenates obtained from various brain regions as well as from liver, kidney, and heart 24 hr after a single i.p. 3NP dose. Mitochondria isolated from forebrains of 3NP-treated rats were also more susceptible to Ca(2+)-induced MPT than those of control rats. We propose that the increased susceptibility of the striatum to 3NP-induced neurodegeneration may be partially explained by its susceptibility to MPT, together with the greater vulnerability of this brain region to glutamate receptor-mediated Ca(2+) influx. SN - 1097-4547 UR - https://www.unboundmedicine.com/medline/citation/19795369/3_nitropropionic_acid_induced_mitochondrial_permeability_transition:_comparative_study_of_mitochondria_from_different_tissues_and_brain_regions_ L2 - https://doi.org/10.1002/jnr.22239 DB - PRIME DP - Unbound Medicine ER -