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STAT5 Reactivation by Catechin Modulates H2O2-Induced Apoptosis Through miR-182/FOXO1 Pathway in SK-N-MC Cells

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Abstract

It has been suggested that oxidative stress-induced apoptosis is a major contributing factor in the pathogenesis of Alzheimer’s and Parkinson’s diseases. However, the molecular mechanism of the oxidative stress-associated apoptosis is far to be elucidated. Herein, we investigated whether STAT5, which is involved in many signaling pathways, is affected by oxidative stress. Previously, it has been shown that STAT5 is a direct activator of miR-182 which is in turn a robust inhibitor of FOXO1. Our results showed that oxidative stress inactivated STAT5 may be in a JAK2-independent manner. Thus, under oxidative stress and miR-182 down-regulation, FOXO1 has the opportunity to be translated leading to FOXO1 over-expression. Finally, pro-apoptotic gene targets of FOXO1 e.g., Bim and Bax are up-regulated leading to apoptosis. To further confirm such events, we also demonstrated that Catechin, a well-known natural antioxidant, partially restored both the STAT5 activation and miR-182 expression resulting in cell survival. To the best of our knowledge, this is the first study demonstrating that STAT5/miRNA-182 negatively regulates FOXO1 in response to oxidative stress.

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Abbreviations

ROS:

Reactive oxygen species

FOXO1:

Forkhead box protein O1

STAT:

Signal transducers and activators of transcription

JAK:

Janus tyrosine kinase

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Acknowledgments

The authors appreciate the financial support of this investigation by the Research Council of University of Tehran.

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

    Ali Gheysarzadeh & Razieh Yazdanparast

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  1. Ali Gheysarzadeh
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Correspondence to Razieh Yazdanparast.

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Gheysarzadeh, A., Yazdanparast, R. STAT5 Reactivation by Catechin Modulates H2O2-Induced Apoptosis Through miR-182/FOXO1 Pathway in SK-N-MC Cells. Cell Biochem Biophys 71, 649–656 (2015). https://doi.org/10.1007/s12013-014-0244-6

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