Different protective roles in vitro of alpha- and beta-domains of growth inhibitory factor (GIF) on neuron injuries caused by oxygen free radicals.
It was well known that beta-amyloid (Abeta) and tau protein play an important role in pathological procedure of Alzheimer's disease (AD), a senile dementia. The growth inhibitory factor (GIF, also named metallothionein-3, MT-3) had been demonstrated to inhibit the outgrowth of cortex neurons in the medium with extract of the AD patient brain. In our experiments, it was found that the neurons of cortex and the PC12 (pheochromocytoma) cells could be protected from the cytotoxicity of beta-amyloid 25-35 in presence of GIF and its domains. Additionally, GIF can scavenge the hydroxyl radical efficiently in CytC-VitC radical producing system and its alpha-domain shown more effective potentials than its beta-domain. The electron paramagnetic resonance spectra also show that the alpha-domain has more potential ability for eliminating reactive oxygen free radicals than its beta-domain. The results suggest that GIF could act as an efficient scavenger against free radicals in vitro and the alpha-domain in GIF molecule shows more potential in protecting against reactive oxygen species injury than the beta-domain.
Ren
H
H
National Laboratory of Protein Engineering, College of Life Sciences, Peking University, Beijing 100871, PR China.
Ji
Q
Q
Liu
Y
Y
Ru
B
B
D000544:Alzheimer Disease / Q000209:etiology; D016229:Amyloid beta-Peptides / Q000633:toxicity; D000818:Animals; D002470:Cell Survival; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects*; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000037:antagonists & inhibitors; D000090023:Metallothionein 3; D008869:Microtubule-Associated Proteins / Q000032:analysis; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D016716:PC12 Cells; D010446:Peptide Fragments / Q000633:toxicity; D051381:Rats
D016229:Amyloid beta-Peptides; D016166:Free Radical Scavengers; D000090023:Metallothionein 3; D008869:Microtubule-Associated Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D017665:Hydroxyl Radical