Scopus İndeksli Yayınlar Koleksiyonu / Scopus Indexed Publications Collection
Permanent URI for this collectionhttps://hdl.handle.net/11147/7148
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Article Citation - WoS: 66Citation - Scopus: 71Lithium Protects Against Paraquat Neurotoxicity by Nrf2 Activation and Mir-34a Inhibition in Sh-Sy5y Cells(Frontiers Media S.A., 2015) Alural, Begüm; Allmer, Jens; Allmer, Jens; Genç, Kürşad; Genç, Şermin; 04.03. Department of Molecular Biology and Genetics; 04. Faculty of Science; 01. Izmir Institute of TechnologyLithium is a mood stabilizing agent commonly used for the treatment of bipolar disorder. Here, we investigated the potential neuroprotective effect of lithium against paraquat toxicity and its underlying mechanisms in vitro. SH-SY5Y human neuroblastoma cells were treated with paraquat (PQ) 0.5 mM concentration after lithium pretreatment to test lithium's capability in preventing cell toxicity. Cell death was evaluated by LDH, WST-8, and tryphan blue assays. Apoptosis was analyzed using DNA fragmentation, Annexin V immunostaining, Sub G1 cell cycle analysis, and caspase-3 activity assays. BCL2, BAX, and NRF2 protein expression were evaluated by Western-blotting and the BDNF protein level was determined with ELISA. mRNA levels of BCL2, BAX, BDNF, and NRF2 target genes (HO-1, GCS, NQO1), as well as miR-34a expression were analyzed by qPCR assay. Functional experiments were done via transfection with NRF2 siRNA and miR-34a mimic. Lithium treatment prevented paraquat induced cell death and apoptosis. Lithium treated cells showed increased anti-apoptotic protein BCL2 and decreased pro-apoptotic protein BAX expression. Lithium exerted a neurotrophic effect by increasing BDNF protein expression. It also diminished reactive oxygen species production and activated the redox sensitive transcription factor NRF2 and increased its target genes expression. Knockdown of NRF2 abolished neuroprotective, anti-apoptotic, and anti-oxidant effects of lithium. Furthermore, lithium significantly decreased both basal and PQ-induced expression of miR-34a. Transfection of miR-34a specific mimic reversed neuroprotective, anti-apoptotic, and anti-oxidant effects of lithium against PQ-toxicity. Our results revealed two novel mechanisms of lithium neuroprotection, namely NRF2 activation and miR-34a suppression.Article Citation - WoS: 19Citation - Scopus: 23Inhibition of Catechol-O (comt) by Some Plant-Derived Alkaloids and Phenolics(Elsevier Ltd., 2010) Yalçın, Dilek; Bayraktar, Oğuz; Bayraktar, Oğuz; 03.02. Department of Chemical Engineering; 03. Faculty of Engineering; 01. Izmir Institute of TechnologyIn this study, as an alternative to the medicines, natural compounds extracted from plant species (Peganum harmala, Cistus parviflorus and Vitex agnus-cactus) were investigated in order to inhibit the catechol-O-metyhltranferase (COMT) activity. In fluorometric enzyme assay, S-adenosylmethionine (SAM) and aesculetin (ES) were used as methyl donor and acceptor substrates, respectively. Their Km values were determined as 3.5 ± 0.3 μM and 6.4 ± 0.4 μM in absence of inhibitor. Inhibition performances of the plant-derived polyphenolics and alkaloids were determined. Inhibitory effect of alkaloids extracted from P. harmala seeds was found the highest among the plant extracts; however, it was lower than that of 3,5-DNC. In case of inhibition mechanism, mixed type inhibition was observed for alkaloid extract whereas uncompetitive inhibition was observed for 3,5-DNC. In case of polyphenolic extracts obtained from C. parviflorus and V. agnus-cactus leaves, mechanism were also explained as mixed type inhibition and their αKi values were calculated as 1.99 ± 0.35 μg/ml and 9.48 ± 0.58 μg/ml, respectively. © 2009 Elsevier B.V. All rights reserved.