A synthetic human proline-rich-polypeptide enhances hydroxyl radical generation and fails to protect dopaminergic neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced toxicity in mice.
Some of the proline-rich-polypeptides (PRPs) are shown to afford protection against spinal cord transection or crush syndrome-induced neurodegeneration in the brain. In the present study a synthetic proline-rich-polypeptide of human hypothalamus origin (h-PRP) has been examined for its potency to protect against dopaminergic neuronal damage caused by the parkinsonian neurotoxin, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Effect of h-PRP on hydroxyl radical (*OH) generation in a Fenton-like reaction was monitored, employing a sensitive salicylate hydroxylation procedure. Balb/c mice treated twice with MPTP (30 mg/kg. i.p., twice, 16 h apart) or h-PRP (20 microg/animal, twice, 16 h apart) showed significant loss of striatal dopamine as assayed by HPLC with electrochemical detection. h-PRP pretreatment failed to attenuate MPTP-induced striatal dopamine depletion. A dose-dependent increase in the generation of *OH by h-PRP suggests its pro-oxidant action, and explains its failure to protect against MPTP-induced parkinsonism in mice.
Knaryan
Varduhi H
VH
H. Buniatian Institute of Biochemistry, Department of Neurohormones Biochemistry, National Academy of Sciences of the Republic of Armenia, 5/1 Paruir Sevak str., 375014 Yerevan, Republic of Armenia.
Samantaray
Supriti
S
Galoyan
Armen A
AA
Mohanakumar
Kochupurackal P
KP
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000494:pharmacology; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D004563:Electrochemistry / Q000379:methods; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism*; D020267:MPTP Poisoning / Q000378:metabolism* / Q000517:prevention & control; D051379:Mice; D008807:Mice, Inbred BALB C; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D011392:Proline / Q000737:chemistry*; D055232:Proline-Rich Protein Domains; D013997:Time Factors; D017211:Treatment Failure
D010455:Peptides; D017665:Hydroxyl Radical; D011392:Proline; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine