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Metallothioneins 1 and 2 attenuate peroxynitrite-induced oxidative stress in Parkinson disease.
Exp Biol Med (Maywood). 2006 Oct; 231(9):1576-83.EB

Abstract

We have examined potent peroxynitrite ion (ONOO-) generator 3-morpholinosydnonimine (SIN-1)-induced neurotoxicity in control wild-type (control(wt)) mice, metallothionein double knockout (MT(dko)) mice, metallothionein-transgenic (MT(trans)) mice, and in cultured human dopaminergic (SK-N-SH) neurons to determine the neuroprotective potential of metallothionein against ONOO(-)-induced neurodegeneration in Parkinson disease (PD). SIN-1-induced lipid peroxidation, reactive oxygen species synthesis, caspase-3 activation, and apoptosis were attenuated by metallothionein gene overexpression and augmented by metallothionein gene down-regulation. A progressive nigrostriatal dopaminergic neurodegeneration in weaver mutant (wv/wv) mice was associated with enhanced nitrite ion synthesis, metallothionein down-regulation, and significantly reduced dopamine synthesis and 18F-DOPA uptake as determined by high-resolution micropositron emission tomography neuroimaging. The striatal (18)F-DOPA uptake was significantly higher in MT(trans) mice than in MT(dko) and alpha-synuclein knockout (alpha-Syn(ko)) mice. These observations provide further evidence that nitric oxide synthase activation and ONOO- synthesis may be involved in the etiopathogenesis of PD, and that metallothionein gene induction may provide neuroprotection.

Authors+Show Affiliations

Department of Pharmacology, University of North Dakota School of Medicine and Health Sciences, 501 North Columbia Road, Grand Forks, ND 58203, USA. mebadi@medicine.nodak.eduNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

17018883

Citation

Ebadi, Manuchair, and Sushil Sharma. "Metallothioneins 1 and 2 Attenuate Peroxynitrite-induced Oxidative Stress in Parkinson Disease." Experimental Biology and Medicine (Maywood, N.J.), vol. 231, no. 9, 2006, pp. 1576-83.
Ebadi M, Sharma S. Metallothioneins 1 and 2 attenuate peroxynitrite-induced oxidative stress in Parkinson disease. Exp Biol Med (Maywood). 2006;231(9):1576-83.
Ebadi, M., & Sharma, S. (2006). Metallothioneins 1 and 2 attenuate peroxynitrite-induced oxidative stress in Parkinson disease. Experimental Biology and Medicine (Maywood, N.J.), 231(9), 1576-83.
Ebadi M, Sharma S. Metallothioneins 1 and 2 Attenuate Peroxynitrite-induced Oxidative Stress in Parkinson Disease. Exp Biol Med (Maywood). 2006;231(9):1576-83. PubMed PMID: 17018883.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Metallothioneins 1 and 2 attenuate peroxynitrite-induced oxidative stress in Parkinson disease. AU - Ebadi,Manuchair, AU - Sharma,Sushil, PY - 2006/10/5/pubmed PY - 2006/10/26/medline PY - 2006/10/5/entrez SP - 1576 EP - 83 JF - Experimental biology and medicine (Maywood, N.J.) JO - Exp Biol Med (Maywood) VL - 231 IS - 9 N2 - We have examined potent peroxynitrite ion (ONOO-) generator 3-morpholinosydnonimine (SIN-1)-induced neurotoxicity in control wild-type (control(wt)) mice, metallothionein double knockout (MT(dko)) mice, metallothionein-transgenic (MT(trans)) mice, and in cultured human dopaminergic (SK-N-SH) neurons to determine the neuroprotective potential of metallothionein against ONOO(-)-induced neurodegeneration in Parkinson disease (PD). SIN-1-induced lipid peroxidation, reactive oxygen species synthesis, caspase-3 activation, and apoptosis were attenuated by metallothionein gene overexpression and augmented by metallothionein gene down-regulation. A progressive nigrostriatal dopaminergic neurodegeneration in weaver mutant (wv/wv) mice was associated with enhanced nitrite ion synthesis, metallothionein down-regulation, and significantly reduced dopamine synthesis and 18F-DOPA uptake as determined by high-resolution micropositron emission tomography neuroimaging. The striatal (18)F-DOPA uptake was significantly higher in MT(trans) mice than in MT(dko) and alpha-synuclein knockout (alpha-Syn(ko)) mice. These observations provide further evidence that nitric oxide synthase activation and ONOO- synthesis may be involved in the etiopathogenesis of PD, and that metallothionein gene induction may provide neuroprotection. SN - 1535-3702 UR - https://www.unboundmedicine.com/medline/citation/17018883/Metallothioneins_1_and_2_attenuate_peroxynitrite_induced_oxidative_stress_in_Parkinson_disease_ L2 - https://journals.sagepub.com/doi/10.1177/153537020623100919?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -