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Mice with a partial deficiency of manganese superoxide dismutase show increased vulnerability to the mitochondrial toxins malonate, 3-nitropropionic acid, and MPTP.
Exp Neurol. 2001 Jan; 167(1):189-95.EN

Abstract

There is substantial evidence implicating mitochondrial dysfunction and free radical generation as major mechanisms of neuronal death in neurodegenerative diseases. The major free radical scavenging enzyme in mitochondria is manganese superoxide dismutase (SOD2). In the present study we investigated the susceptibility of mice with a partial deficiency of SOD2 to the neurotoxins 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), 3-nitropropionic acid (3-NP), and malonate, which are commonly used animal models of Parkinson's and Huntington's disease. Heterozygous SOD2 knockout (SOD2(+/-)) mice showed no evidence of neuropathological or behavioral abnormalities at 2-4 months of age. Compared to littermate wild-type mice, mice with partial SOD2 deficiency showed increased vulnerability to dopamine depletion after systemic MPTP treatment and significantly larger striatal lesions produced by both 3-NP and malonate. SOD2(+/-) mice also showed an increased production of "hydroxyl" radicals after malonate injection measured with the salicylate hydroxyl radical trapping method. These results provide further evidence that reactive oxygen species play an important role in the neurotoxicity of MPTP, malonate, and 3-NP. These findings show that a subclinical deficiency in a free radical scavenging enzyme may act in concert with environmental toxins to produce selective neurodegeneration.

Authors+Show Affiliations

Neurochemistry Laboratory, Massachusetts General Hospital, Boston, Massachusetts, USA.No 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, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11161607

Citation

Andreassen, O A., et al. "Mice With a Partial Deficiency of Manganese Superoxide Dismutase Show Increased Vulnerability to the Mitochondrial Toxins Malonate, 3-nitropropionic Acid, and MPTP." Experimental Neurology, vol. 167, no. 1, 2001, pp. 189-95.
Andreassen OA, Ferrante RJ, Dedeoglu A, et al. Mice with a partial deficiency of manganese superoxide dismutase show increased vulnerability to the mitochondrial toxins malonate, 3-nitropropionic acid, and MPTP. Exp Neurol. 2001;167(1):189-95.
Andreassen, O. A., Ferrante, R. J., Dedeoglu, A., Albers, D. W., Klivenyi, P., Carlson, E. J., Epstein, C. J., & Beal, M. F. (2001). Mice with a partial deficiency of manganese superoxide dismutase show increased vulnerability to the mitochondrial toxins malonate, 3-nitropropionic acid, and MPTP. Experimental Neurology, 167(1), 189-95.
Andreassen OA, et al. Mice With a Partial Deficiency of Manganese Superoxide Dismutase Show Increased Vulnerability to the Mitochondrial Toxins Malonate, 3-nitropropionic Acid, and MPTP. Exp Neurol. 2001;167(1):189-95. PubMed PMID: 11161607.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mice with a partial deficiency of manganese superoxide dismutase show increased vulnerability to the mitochondrial toxins malonate, 3-nitropropionic acid, and MPTP. AU - Andreassen,O A, AU - Ferrante,R J, AU - Dedeoglu,A, AU - Albers,D W, AU - Klivenyi,P, AU - Carlson,E J, AU - Epstein,C J, AU - Beal,M F, PY - 2001/2/13/pubmed PY - 2001/3/10/medline PY - 2001/2/13/entrez SP - 189 EP - 95 JF - Experimental neurology JO - Exp Neurol VL - 167 IS - 1 N2 - There is substantial evidence implicating mitochondrial dysfunction and free radical generation as major mechanisms of neuronal death in neurodegenerative diseases. The major free radical scavenging enzyme in mitochondria is manganese superoxide dismutase (SOD2). In the present study we investigated the susceptibility of mice with a partial deficiency of SOD2 to the neurotoxins 1-methyl-4-phenyl-1,2,5,6-tetrahydropyridine (MPTP), 3-nitropropionic acid (3-NP), and malonate, which are commonly used animal models of Parkinson's and Huntington's disease. Heterozygous SOD2 knockout (SOD2(+/-)) mice showed no evidence of neuropathological or behavioral abnormalities at 2-4 months of age. Compared to littermate wild-type mice, mice with partial SOD2 deficiency showed increased vulnerability to dopamine depletion after systemic MPTP treatment and significantly larger striatal lesions produced by both 3-NP and malonate. SOD2(+/-) mice also showed an increased production of "hydroxyl" radicals after malonate injection measured with the salicylate hydroxyl radical trapping method. These results provide further evidence that reactive oxygen species play an important role in the neurotoxicity of MPTP, malonate, and 3-NP. These findings show that a subclinical deficiency in a free radical scavenging enzyme may act in concert with environmental toxins to produce selective neurodegeneration. SN - 0014-4886 UR - https://www.unboundmedicine.com/medline/citation/11161607/Mice_with_a_partial_deficiency_of_manganese_superoxide_dismutase_show_increased_vulnerability_to_the_mitochondrial_toxins_malonate_3_nitropropionic_acid_and_MPTP_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0014-4886(00)97525-3 DB - PRIME DP - Unbound Medicine ER -