STAT5 reactivation by catechin modulates H2O 2-induced apoptosis through miR-182/FOXO1 pathway in SK-N-MC cells.
Cell Biochem Biophys
; 71(2): 649-56, 2015 Mar.
Article
in En
| MEDLINE
| ID: mdl-25231457
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Catechin
/
Apoptosis
/
MicroRNAs
/
STAT5 Transcription Factor
/
Forkhead Transcription Factors
/
Antioxidants
Limits:
Humans
Language:
En
Journal:
Cell Biochem Biophys
Journal subject:
BIOFISICA
/
BIOQUIMICA
Year:
2015
Document type:
Article
Affiliation country:
Irán