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Arylpiperazine Dopamineric Ligands Protect Neuroblastoma Cells from Nitric Oxide (NO)‐Induced Mitochondrial Damage and Apoptosis
Author(s) -
Tovilovic Gordana,
Zogovic Nevena,
HarhajiTrajkovic Ljubica,
MisirkicMarjanovic Maja,
Janjetovic Kristina,
Vucicevic Ljubica,
KosticRajacic Sladjana,
Schrattenholz Andre,
Isakovic Aleksandra,
Soskic Vukic,
Trajkovic Vladimir
Publication year - 2012
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201100537
Subject(s) - neuroprotection , chemistry , nitric oxide , neurotoxicity , sh sy5y , apoptosis , pharmacology , protein kinase b , depolarization , dopaminergic , oxidative stress , pi3k/akt/mtor pathway , microbiology and biotechnology , biochemistry , dopamine , neuroblastoma , biophysics , biology , cell culture , endocrinology , toxicity , genetics , organic chemistry
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 D 1 /D 2 receptor blocker butaclamol. These results reported support the further study of arylpiperazines as potential neuroprotective agents.