The mechanisms responsible for neuroprotective capacity of arylpiperazine dopaminergic ligands against cell death induced by sodium nitroprusside
| Autor: | Marija Slavić, Mirko Tomić, Aleksandra Nikolić-Kokić, Deana Andrić, Đurđica Ignjatović, Danijela Vojnović Milutinović, Slađana Kostić-Rajačić |
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| Rok vydání: | 2012 |
| Předmět: |
Agonist
Nitroprusside medicine.drug_class Parkinson's disease Nerve Tissue Proteins CHO Cells Pharmacology Ligands Dopamine agonist Neuroprotection Piperazines Cell Line 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cricetulus Cricetinae medicine Animals Humans Protein Isoforms Nitric Oxide Donors Viability assay Receptor 030304 developmental biology Neurons 0303 health sciences Cell Death Chemistry Receptors Dopamine D2 Dopaminergic Glutathione Recombinant Proteins Arylpiperazines Dopamine D2 Receptor Antagonists Oxidative Stress Neuroprotective Agents Oxidative stress Dopamine Agonists Dopamine Antagonists Sodium nitroprusside 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | European Journal of Pharmacology |
| Popis: | 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. (C) 2012 Elsevier B.V. All rights reserved. |
| Databáze: | OpenAIRE |
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