title: Vinpocetine and Vasoactive Intestinal Peptide Attenuate Manganese-Induced Toxicity in NE-4C Cells.
abstract: Increased concentration of manganese (Mn) in the brain is known to be associated with excitotoxicity and neuroinflammation. Vinpocetine, an alkaloid derived from the plant Vinca minor L., basically shows its effect via phosphodiesterase inhibition and voltage-dependent Na+channels. Vasoactive intestinal peptide (VIP) has gastrointestinal, vasomotor, muscular, and neuroprotective effects. The aim of this study was to examine the potential protective effects of vinpocetine and VIP against Mn toxicity in NE-4C neural stem cells (NSCs). VIP treatment at 1 μM and vinpocetine treatment at 2 μM concentrations were sufficient to yield maximum protection, and these concentrations were adopted in the following experiments. In this study, Mn treatment significantly increased lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) production, and triggered cell death in NE-4C cultures. However, significant reduction in LDH release was observed following vinpocetine or VIP treatments when compared with control. Similar to these findings, vinpocetine or VIP treatments significantly reduced membrane degradation induced by Mn (p < 0.001). Moreover, vinpocetine attenuated Mn-induced decrease of mitochondrial membrane potential. Similarly, proapoptotic protein bax and ROS production significantly decreased in cells after incubation with vinpocetine (p = 0.01) or VIP in the presence of Mn (p < 0.001). Our study provides the evidence that both vinpocetine and VIP may exert protective effects via modulating oxidative stress and apoptosis in Mn-induced neurodegeneration in NE-4C cells.
authors.affiliation: Department of Physiology, School of Medicine, Faculty of Medicine, Ege University, 35100, Bornova, Izmir, Turkey. saylavbora@hotmail.com.
authors.forename: Saylav
authors.initials: S
authors.lastname: Bora
authors.affiliation: Department of Physiology, School of Medicine, Faculty of Medicine, Ege University, 35100, Bornova, Izmir, Turkey.
authors.forename: Mumin Alper
authors.initials: MA
authors.lastname: Erdogan
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Ege University, 35100, Bornova, Izmir, Turkey.
authors.forename: Güliz
authors.initials: G
authors.lastname: Armagan
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Ege University, 35100, Bornova, Izmir, Turkey.
authors.forename: Elvin
authors.initials: E
authors.lastname: Sevgili
authors.affiliation: Department of Physiology, School of Medicine, Faculty of Medicine, Ege University, 35100, Bornova, Izmir, Turkey.
authors.forename: Taner
authors.initials: T
authors.lastname: Dagcı
mesh_terms: D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008345:Manganese / Q000633:toxicity*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects*; D058953:Neural Stem Cells; D017382:Reactive Oxygen Species / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000494:pharmacology*; D014748:Vinca Alkaloids / Q000494:pharmacology*
chemical_list: D017382:Reactive Oxygen Species; D014748:Vinca Alkaloids; D014660:Vasoactive Intestinal Peptide; D008345:Manganese; C013983:vinpocetine
keywords: Apoptosis; Manganese; NE-4C cells; Vasoactive intestinal peptide; Vinpocetine