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Synthetic bovine proline-rich-polypeptides generate hydroxyl radicals and fail to protect dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity in mice.
Neuropeptides. 2006 Aug; 40(4):291-8.N

Abstract

Proline-rich-polypeptides (PRPs) isolated from bovine hypothalamus have been shown to render protection against neuronal injury of the brain and spinal cord. We examined two PRPs containing 15 and 10 amino acid residues (PRP-1 and PRP-4 synthetic polypeptide) for their effect, if any, on dopaminergic neuronal damage caused by the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Effects of these PRPs on hydroxyl radical ((*)OH) generation in a Fenton-like reaction as well as from isolated mitochondria were monitored, employing a sensitive salicylate hydroxylation procedure. Balb/c mice treated (i.p., twice, 16 h apart) with MPTP (30 mg/kg) or PRP-1 (1.6 mg/kg), but not PRP-4 (1.6 mg/kg) showed significant loss of striatal dopamine and norepinephrine as assayed by an HPLC-electrochemical procedure. Pretreatment with the PRPs, 30 min prior to the neurotoxin administration failed to attenuate MPTP-induced striatal dopamine or norepinephrine depletion, but significantly attenuated the MPTP-induced decrease in dopamine turnover. A significant increase in the generation of (*)OH by the PRPs in a Fenton-like reaction or from isolated mitochondria suggests their pro-oxidant action, and explains their failure to protect against MPTP-induced parkinsonism in mice.

Authors+Show Affiliations

Division of Clinical and Experimental Neuroscience, Indian Institute of Chemical Biology, Jadavpur, Kolkata 700 032, West Bengal, India.No 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

Language

eng

PubMed ID

16712929

Citation

Knaryan, Varduhi H., et al. "Synthetic Bovine Proline-rich-polypeptides Generate Hydroxyl Radicals and Fail to Protect Dopaminergic Neurons Against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Dopaminergic Neurotoxicity in Mice." Neuropeptides, vol. 40, no. 4, 2006, pp. 291-8.
Knaryan VH, Samantaray S, Varghese M, et al. Synthetic bovine proline-rich-polypeptides generate hydroxyl radicals and fail to protect dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity in mice. Neuropeptides. 2006;40(4):291-8.
Knaryan, V. H., Samantaray, S., Varghese, M., Srinivasan, A., Galoyan, A. A., & Mohanakumar, K. P. (2006). Synthetic bovine proline-rich-polypeptides generate hydroxyl radicals and fail to protect dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity in mice. Neuropeptides, 40(4), 291-8.
Knaryan VH, et al. Synthetic Bovine Proline-rich-polypeptides Generate Hydroxyl Radicals and Fail to Protect Dopaminergic Neurons Against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Dopaminergic Neurotoxicity in Mice. Neuropeptides. 2006;40(4):291-8. PubMed PMID: 16712929.
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TY - JOUR T1 - Synthetic bovine proline-rich-polypeptides generate hydroxyl radicals and fail to protect dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced dopaminergic neurotoxicity in mice. AU - Knaryan,Varduhi H, AU - Samantaray,Supriti, AU - Varghese,Merina, AU - Srinivasan,Ambika, AU - Galoyan,Armen A, AU - Mohanakumar,Kochupurackal P, Y1 - 2006/05/18/ PY - 2005/10/05/received PY - 2006/03/21/revised PY - 2006/03/25/accepted PY - 2006/5/23/pubmed PY - 2007/3/16/medline PY - 2006/5/23/entrez SP - 291 EP - 8 JF - Neuropeptides JO - Neuropeptides VL - 40 IS - 4 N2 - Proline-rich-polypeptides (PRPs) isolated from bovine hypothalamus have been shown to render protection against neuronal injury of the brain and spinal cord. We examined two PRPs containing 15 and 10 amino acid residues (PRP-1 and PRP-4 synthetic polypeptide) for their effect, if any, on dopaminergic neuronal damage caused by the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Effects of these PRPs on hydroxyl radical ((*)OH) generation in a Fenton-like reaction as well as from isolated mitochondria were monitored, employing a sensitive salicylate hydroxylation procedure. Balb/c mice treated (i.p., twice, 16 h apart) with MPTP (30 mg/kg) or PRP-1 (1.6 mg/kg), but not PRP-4 (1.6 mg/kg) showed significant loss of striatal dopamine and norepinephrine as assayed by an HPLC-electrochemical procedure. Pretreatment with the PRPs, 30 min prior to the neurotoxin administration failed to attenuate MPTP-induced striatal dopamine or norepinephrine depletion, but significantly attenuated the MPTP-induced decrease in dopamine turnover. A significant increase in the generation of (*)OH by the PRPs in a Fenton-like reaction or from isolated mitochondria suggests their pro-oxidant action, and explains their failure to protect against MPTP-induced parkinsonism in mice. SN - 0143-4179 UR - https://www.unboundmedicine.com/medline/citation/16712929/Synthetic_bovine_proline_rich_polypeptides_generate_hydroxyl_radicals_and_fail_to_protect_dopaminergic_neurons_against_1_methyl_4_phenyl_1236_tetrahydropyridine_induced_dopaminergic_neurotoxicity_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0143-4179(06)00030-8 DB - PRIME DP - Unbound Medicine ER -