Arylpiperazine dopamineric ligands protect neuroblastoma cells from nitric oxide (NO)-induced mitochondrial damage and apoptosis
2012
Authors:
Tovilović-Kovačević, GordanaZogović, Nevena
Harhaji-Trajković, Ljubica
Misirkić Marjanović, Maja
Janjetović, Kristina
Vučićević, Ljubica
Kostić-Rajačić, Slađana
Schrattenholz, Andre
Isaković, Aleksandra
Šoškić, Vukić
Trajković, Vladimir
Document Type:
Article (Published version)
,
2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Metadata
Show full item recordAbstract:
The protective ability of novel arylpiperazine-based dopaminergic ligands against nitric oxide (NO)-mediated neurotoxicity is investigated. The most potent neuroprotective arylpiperazine identified during the study was N-{4-[2-(4-phenyl-piperazin-1-yl)ethyl]-phenyl}picolinamide, which protected SH-SY5Y human neuron-like cells from the proapoptotic effect of NO donor sodium nitroprusside (SNP) by decreasing oxidative stress, mitochondrial membrane depolarization, caspase activation and subsequent phosphatydilserine externalization/DNA fragmentation. The protective effect was associated with the inhibition of proapoptotic (JNK, ERK, AMPK) and activation of antiapoptotic (Akt) signaling pathways, in the absence of interference with intracellular NO accumulation. The neuroprotective action of arylpiperazines was shown to be independent of dopamine receptor binding, as it was not affected by the high-affinity D₁/D₂ receptor blocker butaclamol. These results reported support the further study of arylpiperazines as potential neuroprotective agents.
Keywords:
apoptosis; dopaminergic ligands; neuroprotection; nitric oxide; nitrogenSource:
ChemMedChem, 2012, 7, 3, 495-508Funding / projects:
- Modulation of intracellular energy balance-controlling signalling pathways in therapy of cancer and neuro-immuno-endocrine disorders (RS-MESTD-Integrated and Interdisciplinary Research (IIR or III)-41025)
DOI: 10.1002/cmdc.201100537
ISSN: 1860-7179
PubMed: 22298298