Sepantronium Bromide (Ym155), a Small Molecule Survivin Inhibitor, Promotes Apoptosis by Induction of Oxidative Stress, Worsens the Behavioral Deficits and Develops an Early Model of Toxic Demyelination: In Vivo and In-Silico Study

Sepantronium Bromide (Ym155), a Small Molecule Survivin Inhibitor, Promotes Apoptosis by Induction of Oxidative Stress, Worsens the Behavioral Deficits and Develops an Early Model of Toxic Demyelination: In Vivo and In-Silico Study Publisher Pubmed

Reiszadehjahromi S¹ ; Sepand MR² ; Ramezanisefidar S³ ; Shahlaei M⁴ ; Moradi S⁴ ; Yazdankhah M⁵ ; Sanadgol N⁶

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1. Department of Biology, University of Sistan and Baluchestan, Zahedan, Iran
2. Department of Toxicology and Pharmacology, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
3. Department of Biology, Faculty of Basic Sciences, Razi University, Kermanshah, Iran
4. Nano Drug Delivery Research Center, School of Pharmacy, Kermanshah University of Medical Science, Kermanshah, Iran
5. Department of Ophthalmology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States
6. Department of Biology, Faculty of Sciences, University of Zabol, Zabol, Iran

Source: Neurochemical Research Published:2019

Abstract

Cuprizone (cup) model targets oligodendrocytes (OLGs) degeneration and is frequently used for the mechanistic understanding of de- and remyelination. Improperly, this classic model is time-consuming and the extent of brain lesions and behavioral deficits are changeable (both temporally and spatially) within a mouse strain. We aimed to offer an alternative, less time-consuming, and more reproducible cup model. Mice (C57BL/6) were treated with cup (400 mg kg−1 day−1/gavage) for three consecutive weeks to induce OLGs degeneration with or without YM155 (1 mg kg−1 day−1) to examine the effects of this molecule in cup neurotoxicity. Co-administration of cup and YM155 (cuYM) accelerated the intrinsic apoptosis of mature OLGs (MOG positive cells) through the upregulation of caspase-9 and caspase-3. In addition to the stimulation of oxidative stress via reduction of glutathione peroxidase and induction of malondialdehyde, behavioral deficits in both Open-field and Rota-rod tests were worsened by cuYM. In the cuYM group, the expression of BIRC5, BIRC4 and NAIP was reduced, but no significant changes were observed in the abundance of the other inhibitor of apoptosis proteins (cIAP1 and cIAP2) in comparison with the cup group. Moreover, in silico analysis validated that YM155 directly interrupts the binding sites of certain transcription factors, such as kruppel-like family (Klf), specificity proteins (SPs), myeloid zinc fingers (MZFs), zinc finger proteins (ZNFPs), and transcription factor activating enhancer-binding proteins (TFAPs), on the promoters of target genes. In conclusion, this modified model promotes cup-induced redox and apoptosis signaling, elevates behavioral deficits, saves time, minimizes variations, and can be employed for early evaluation of novel neuroprotective agents in oligodendropathies. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.

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Style	Citing Format
MLA	Reiszadehjahromi S, et al.. "Sepantronium Bromide (Ym155), a Small Molecule Survivin Inhibitor, Promotes Apoptosis by Induction of Oxidative Stress, Worsens the Behavioral Deficits and Develops an Early Model of Toxic Demyelination: In Vivo and In-Silico Study." Neurochemical Research, vol. 44, no. 11, 2019, pp. 2482-2498.
APA	Reiszadehjahromi S, Sepand MR, Ramezanisefidar S, Shahlaei M, Moradi S, Yazdankhah M, Sanadgol N (2019). Sepantronium Bromide (Ym155), a Small Molecule Survivin Inhibitor, Promotes Apoptosis by Induction of Oxidative Stress, Worsens the Behavioral Deficits and Develops an Early Model of Toxic Demyelination: In Vivo and In-Silico Study. Neurochemical Research, 44(11), 2482-2498.
Chicago	Reiszadehjahromi S, Sepand MR, Ramezanisefidar S, Shahlaei M, Moradi S, Yazdankhah M, Sanadgol N. "Sepantronium Bromide (Ym155), a Small Molecule Survivin Inhibitor, Promotes Apoptosis by Induction of Oxidative Stress, Worsens the Behavioral Deficits and Develops an Early Model of Toxic Demyelination: In Vivo and In-Silico Study." Neurochemical Research 44, no. 11 (2019): 2482-2498.
Harvard	Reiszadehjahromi S et al. (2019) 'Sepantronium Bromide (Ym155), a Small Molecule Survivin Inhibitor, Promotes Apoptosis by Induction of Oxidative Stress, Worsens the Behavioral Deficits and Develops an Early Model of Toxic Demyelination: In Vivo and In-Silico Study', Neurochemical Research, 44(11), pp. 2482-2498.
Vancouver	Reiszadehjahromi S, Sepand MR, Ramezanisefidar S, Shahlaei M, Moradi S, Yazdankhah M, et al.. Sepantronium Bromide (Ym155), a Small Molecule Survivin Inhibitor, Promotes Apoptosis by Induction of Oxidative Stress, Worsens the Behavioral Deficits and Develops an Early Model of Toxic Demyelination: In Vivo and In-Silico Study. Neurochemical Research. 2019;44(11):2482-2498.
BibTex	@article{ author = {Reiszadehjahromi S and Sepand MR and Ramezanisefidar S and Shahlaei M and Moradi S and Yazdankhah M and Sanadgol N}, title = {Sepantronium Bromide (Ym155), a Small Molecule Survivin Inhibitor, Promotes Apoptosis by Induction of Oxidative Stress, Worsens the Behavioral Deficits and Develops an Early Model of Toxic Demyelination: In Vivo and In-Silico Study}, journal = {Neurochemical Research}, volume = {44}, number = {11}, pages = {2482-2498}, year = {2019} }
RIS	TY - JOUR AU - Reiszadehjahromi S AU - Sepand MR AU - Ramezanisefidar S AU - Shahlaei M AU - Moradi S AU - Yazdankhah M AU - Sanadgol N TI - Sepantronium Bromide (Ym155), a Small Molecule Survivin Inhibitor, Promotes Apoptosis by Induction of Oxidative Stress, Worsens the Behavioral Deficits and Develops an Early Model of Toxic Demyelination: In Vivo and In-Silico Study JO - Neurochemical Research VL - 44 IS - 11 SP - 2482 EP - 2498 PY - 2019 ER -

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