Protective effect of a triazine-derivative (AA3E2) on beta-amyloid-induced damages in SK-N-MC cells.
The role of beta-amyloid (A beta) in the pathogenesis of Alzheimer's disease (AD) is frequently reported in the literature. Though the exact mode of action is not known, it is suggested that A beta induces cell death through induction of oxidative stress possibly through hydrogen peroxide generation. In that case, antioxidants should be capable of attenuating the A beta-induced cytotoxicities. In that regard, we evaluated the effect(s) of a triazine-derivative, AA3E2, with established antioxidant activity. Pretreatment of SK-N-MC neuroblastoma cells with AA3E2, followed by exposure to A beta(1-42) showed 28.3% higher viability relative to the control cells which has not been treated with AA3E2. In addition, AA3E2 inhibited caspase-3 activation caused by A beta(1-42) and it attenuated A beta(1-42)-induced intracellular ROS (reactive oxygen species) accumulation. The lower level of intracellular free radicals was further confirmed by higher and lower activities of intracellular catalase and superoxide dismutase, respectively. These observations, parallel to the literature data, reconfirm the oxidative stress disrupting role of A beta(1-42) peptide. Thus, sequestration of this role by potential antioxidants such as AA3E2 might happen to be a suitable strategy for future treatments of AD.
Yazdanparast
Razieh
R
Institute of Biochemistry and Biophysics, University of Tehran, P.O. Box 13145-1384, Tehran, Iran. yazdan@ibb.ut.ac.ir
Shaykhalishahi
Hamed
H
D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000633:toxicity*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000633:toxicity*; D017382:Reactive Oxygen Species / Q000378:metabolism; D013482:Superoxide Dismutase / Q000378:metabolism; D014227:Triazines / Q000737:chemistry / Q000494:pharmacology*
D016229:Amyloid beta-Peptides; D000975:Antioxidants; C545493:N-(2-(2-(2-aminoethoxy)ethoxy)ethyl)-N-butyl-6-decyl-1,3,5-triazine-2,4-diamine; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; D014227:Triazines; C075222:amyloid beta-protein (1-42); D002374:Catalase; D013482:Superoxide Dismutase; D053148:Caspase 3