Tags

Type your tag names separated by a space and hit enter

Manganese superoxide dismutase overexpression attenuates MPTP toxicity.
Neurobiol Dis. 1998 Oct; 5(4):253-8.ND

Abstract

There is substantial evidence implicating mitochondrial dysfunction and free radical generation in the neurotoxicity of MPTP. Manganese superoxide dismutase (MnSOD) is the primary antioxidant enzyme protecting against superoxide radicals produced within mitochondria. Overexpression of human MnSOD in transgenic mice resulted in increased MnSOD localized to mitochondria in neurons and a 50% increase in total MnSOD activity in brain homogenates. We found that MPTP toxicity was significantly attenuated in the MnSOD transgenic mice which overexpress the human manganese superoxide dismutase gene, with these mice showing threefold greater dopamine levels than controls following MPTP. There were no alterations in MPP+ levels, suggesting that the effects were not due to altered metabolism of MPTP. A significant increase in 3-nitrotyrosine levels was seen in littermate controls but not in transgenic mice overexpressing human MnSOD. These results provide further evidence implicating mitochondrial dysfunction and oxidative damage in the pathogenesis of MPTP neurotoxicity.

Authors+Show Affiliations

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

Language

eng

PubMed ID

9848095

Citation

Klivenyi, P, et al. "Manganese Superoxide Dismutase Overexpression Attenuates MPTP Toxicity." Neurobiology of Disease, vol. 5, no. 4, 1998, pp. 253-8.
Klivenyi P, St Clair D, Wermer M, et al. Manganese superoxide dismutase overexpression attenuates MPTP toxicity. Neurobiol Dis. 1998;5(4):253-8.
Klivenyi, P., St Clair, D., Wermer, M., Yen, H. C., Oberley, T., Yang, L., & Flint Beal, M. (1998). Manganese superoxide dismutase overexpression attenuates MPTP toxicity. Neurobiology of Disease, 5(4), 253-8.
Klivenyi P, et al. Manganese Superoxide Dismutase Overexpression Attenuates MPTP Toxicity. Neurobiol Dis. 1998;5(4):253-8. PubMed PMID: 9848095.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Manganese superoxide dismutase overexpression attenuates MPTP toxicity. AU - Klivenyi,P, AU - St Clair,D, AU - Wermer,M, AU - Yen,H C, AU - Oberley,T, AU - Yang,L, AU - Flint Beal,M, PY - 1998/12/16/pubmed PY - 1998/12/16/medline PY - 1998/12/16/entrez SP - 253 EP - 8 JF - Neurobiology of disease JO - Neurobiol Dis VL - 5 IS - 4 N2 - There is substantial evidence implicating mitochondrial dysfunction and free radical generation in the neurotoxicity of MPTP. Manganese superoxide dismutase (MnSOD) is the primary antioxidant enzyme protecting against superoxide radicals produced within mitochondria. Overexpression of human MnSOD in transgenic mice resulted in increased MnSOD localized to mitochondria in neurons and a 50% increase in total MnSOD activity in brain homogenates. We found that MPTP toxicity was significantly attenuated in the MnSOD transgenic mice which overexpress the human manganese superoxide dismutase gene, with these mice showing threefold greater dopamine levels than controls following MPTP. There were no alterations in MPP+ levels, suggesting that the effects were not due to altered metabolism of MPTP. A significant increase in 3-nitrotyrosine levels was seen in littermate controls but not in transgenic mice overexpressing human MnSOD. These results provide further evidence implicating mitochondrial dysfunction and oxidative damage in the pathogenesis of MPTP neurotoxicity. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/9848095/Manganese_superoxide_dismutase_overexpression_attenuates_MPTP_toxicity_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969996198901917 DB - PRIME DP - Unbound Medicine ER -