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Flavonoid Baicalein Modulates H2O2-Induced Mitogen-Activated Protein Kinases Activation and Cell Death in SK-N-MC Cells

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Abstract

It is believed that ROS-induced oxidative stress triggers numerous signaling pathways which are involved in neurodegenerative diseases, including Alzheimer’s disease. To find the effective drugs for neurodegenerative diseases, the deep delve into molecular mechanisms underlie these diseases is necessary. In the current study, we investigated the effects of flavonoid baicalein on H2O2-induced oxidative stress and cell death in SK-N-MC cells. Our results revealed that the treatment of SK-N-MC cells with H2O2 led to a decrease in cell viability through phosphorylation and activation of extracellular signal-regulated kinases (ERKs) and c-Jun N-terminal kinases (JNKs) pathways followed by increase in Bax/Bcl2 ratio and initiation of caspase-dependent apoptotic pathways. In addition, our results showed that the exposure of SK-N-MC cells to H2O2 ended up in reduction of glutathione (GSH) levels of SK-N-MC cells via JNK/ERK-mediated down-regulation of γ-glutamyl-cysteine synthetase (γ-GCS) expression. Our results demonstrated that flavonoid baicalein protected against H2O2-induced cell death by inhibition of JNK/ERK pathways activation and other key molecules in apoptotic pathways, including blockage of Bax and caspase-9 activation, induction of Bcl-2 expression and prevention of cell death. Baicalein supported intracellular defense mechanisms through maintaining GSH levels in SK-N-MC cells by the removal of inhibition effects of JNK/ERK pathways from γ-GCS expression. In addition, baicalein attenuated lipid and protein peroxidation and intracellular reactive oxygen species in SK-N-MC cells. In accordance with these observations, baicalein can be a promising candidate in antioxidant therapy and designing of natural-based drug for ROS-induced neurodegenerative disorders.

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Abbreviations

DTNB:

Dithionitrobenzoic acid

γ-GCS:

γ-Glutamyl-cysteine synthetase

MDA:

Malondialdehyde

MTT:

3-(4,5-Dimethylthiazol-2-yl)-2, 5-diphenyl tetrazolium bromide

mBCL:

Monochlorobimane

PBS:

Phosphate buffer saline

PCO:

Protein carbonyl

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Acknowledgment

The author appreciates the financial support of this investigation by the Research Council of University of Tehran.

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Authors and Affiliations

  1. Institute of Biochemistry and Biophysics, University of Tehran, P.O. Box 13145-1384, Tehran, Iran

    Maryam Moslehi, Azadeh Meshkini & Razieh Yazdanparast

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  1. Maryam Moslehi
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  2. Azadeh Meshkini
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  3. Razieh Yazdanparast
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Correspondence to Razieh Yazdanparast.

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Moslehi, M., Meshkini, A. & Yazdanparast, R. Flavonoid Baicalein Modulates H2O2-Induced Mitogen-Activated Protein Kinases Activation and Cell Death in SK-N-MC Cells. Cell Mol Neurobiol 32, 549–560 (2012). https://doi.org/10.1007/s10571-011-9795-x

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