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The mechanisms responsible for neuroprotective capacity of arylpiperazine dopaminergic ligands against cell death induced by sodium nitroprusside.
MedLine Citation:
PMID:  22449382     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
A group of sixteen arylpiperazines had been previously synthesized and evaluated for atypical antipsychotic activity. Here we examined these compounds for their neuroprotective capacity. The affinity and agonist/antagonist action of the arylpiperazines at dopamine hD(2S) receptors were determined in vitro on membranes from stably transfected CHO-hD(2S) cell line. The assays for cell viability and antioxidative capacity (total glutathione and total superoxide dismutase activity), amount of nitric oxide and superoxide radicals, as well as influence on prosurvival pathways (Akt and ERK), were performed on the human neuroblastoma cell line SH-SY5Y. Cell death was induced by oxidative or nitrosative stress, or by growing cells in the medium deprived of serum. Only four of the arylpiperazines exhibited notable neuroprotection against cell death induced by sodium nitroprusside. Two of these arylpiperazines induced elevations of pAkt, while two other compounds reduced the levels of pErk, whereas these actions are considered to support the cell survival. The benzimidazole heteroaryl-group, that mimics catechol moiety of the dopamine molecule, might be the prerequisite structure for the neuroprotective action of these ligands. It is postulated that neuroprotection was acquired also by elevation of endogenous glutathione or total superoxide dismutase activity.
Authors:
Durđica Ignjatović; Danijela Vojnović Milutinović; Aleksandra Nikolić-Kokić; Marija Slavić; Deana Andrić; Mirko Tomić; Slađana Kostić-Rajačić
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-3-17
Journal Detail:
Title:  European journal of pharmacology     Volume:  -     ISSN:  1879-0712     ISO Abbreviation:  -     Publication Date:  2012 Mar 
Date Detail:
Created Date:  2012-3-27     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  1254354     Medline TA:  Eur J Pharmacol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012. Published by Elsevier B.V.
Affiliation:
Department of Biochemistry, Institute for Biological Research, University of Belgrade, 142 Despot Stefana Blvd., 11060 Belgrade, Serbia.
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