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Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis

Authorized Users Only
2012
Authors
Tovilović, Gordana
Zogovic, Nevena
Harhaji-Trajković, Ljubica
Misirkić-Marjanović, Maja
Janjetovic, Kristina
Vucicevic, Ljubica
Kostić Rajačić, Slađana
Schrattenholz, Andre
Isaković, Aleksandra
Šoškić, Vukić
Trajković, Vladimir
Article (Published version)
Metadata
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Abstract
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 stud...y of arylpiperazines as potential neuroprotective agents.

Keywords:
apoptosis / dopaminergic ligands / neuroprotection / nitric oxide / nitrogen heterocycles
Source:
Chemmedchem, 2012, 7, 3, 495-508
Publisher:
  • Wiley-V C H Verlag Gmbh, Weinheim
Funding / projects:
  • Modulation of intracellular energy balance-controlling signalling pathways in therapy of cancer and neuro-immuno-endocrine disorders (RS-41025)

DOI: 10.1002/cmdc.201100537

ISSN: 1860-7179

PubMed: 22298298

WoS: 000300942300017

Scopus: 2-s2.0-84857772680
[ Google Scholar ]
8
9
URI
https://cer.ihtm.bg.ac.rs/handle/123456789/1037
Collections
  • Radovi istraživača / Researchers' publications
Institution/Community
IHTM
TY  - JOUR
AU  - Tovilović, Gordana
AU  - Zogovic, Nevena
AU  - Harhaji-Trajković, Ljubica
AU  - Misirkić-Marjanović, Maja
AU  - Janjetovic, Kristina
AU  - Vucicevic, Ljubica
AU  - Kostić Rajačić, Slađana
AU  - Schrattenholz, Andre
AU  - Isaković, Aleksandra
AU  - Šoškić, Vukić
AU  - Trajković, Vladimir
PY  - 2012
UR  - https://cer.ihtm.bg.ac.rs/handle/123456789/1037
AB  - 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.
PB  - Wiley-V C H Verlag Gmbh, Weinheim
T2  - Chemmedchem
T1  - Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis
VL  - 7
IS  - 3
SP  - 495
EP  - 508
DO  - 10.1002/cmdc.201100537
ER  - 
@article{
author = "Tovilović, Gordana and Zogovic, Nevena and Harhaji-Trajković, Ljubica and Misirkić-Marjanović, Maja and Janjetovic, Kristina and Vucicevic, Ljubica and Kostić Rajačić, Slađana and Schrattenholz, Andre and Isaković, Aleksandra and Šoškić, Vukić and Trajković, Vladimir",
year = "2012",
abstract = "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.",
publisher = "Wiley-V C H Verlag Gmbh, Weinheim",
journal = "Chemmedchem",
title = "Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis",
volume = "7",
number = "3",
pages = "495-508",
doi = "10.1002/cmdc.201100537"
}
Tovilović, G., Zogovic, N., Harhaji-Trajković, L., Misirkić-Marjanović, M., Janjetovic, K., Vucicevic, L., Kostić Rajačić, S., Schrattenholz, A., Isaković, A., Šoškić, V.,& Trajković, V.. (2012). Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis. in Chemmedchem
Wiley-V C H Verlag Gmbh, Weinheim., 7(3), 495-508.
https://doi.org/10.1002/cmdc.201100537
Tovilović G, Zogovic N, Harhaji-Trajković L, Misirkić-Marjanović M, Janjetovic K, Vucicevic L, Kostić Rajačić S, Schrattenholz A, Isaković A, Šoškić V, Trajković V. Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis. in Chemmedchem. 2012;7(3):495-508.
doi:10.1002/cmdc.201100537 .
Tovilović, Gordana, Zogovic, Nevena, Harhaji-Trajković, Ljubica, Misirkić-Marjanović, Maja, Janjetovic, Kristina, Vucicevic, Ljubica, Kostić Rajačić, Slađana, Schrattenholz, Andre, Isaković, Aleksandra, Šoškić, Vukić, Trajković, Vladimir, "Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)-Induced Mitochondrial Damage and Apoptosis" in Chemmedchem, 7, no. 3 (2012):495-508,
https://doi.org/10.1002/cmdc.201100537 . .

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