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

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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 heterocyclesSource:
Chemmedchem, 2012, 7, 3, 495-508Publisher:
- Wiley-V C H Verlag Gmbh, Weinheim
Funding / projects:
DOI: 10.1002/cmdc.201100537
ISSN: 1860-7179
PubMed: 22298298
WoS: 000300942300017
Scopus: 2-s2.0-84857772680
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IHTMTY - 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 . .