Expression of PUMA in Follicular Granulosa Cells Regulated by FoxO1 Activation During Oxidative Stress. (June 2015)

• Record Type: Journal Article
• Authors: Liu, Ze-Qun; Shen, Ming; Wu, Wang-Jun; Li, Bo-Jiang; Weng, Qian-Nan; Li, Mei; Liu, Hong-Lin
• Is Part Of: Reproductive sciences. Volume 22:Number 6(2015:Jun.)
• Page Start: 696
• Page End: 705
• Publication Date: 2015-06
• Subjects: follicular atresia -- apoptosis -- PUMA -- FoxO1 -- oxidative stress -- granulosa cell; Reproductive health -- Periodicals; Reproduction -- Periodicals; 612.6
• DOI: 10.1177/1933719114556483
• Languages: English
• ISSNs: 1933-7191

Abstract

Many studies have demonstrated that oxidative stress-induced apoptosis is a main cause of follicular atresia. Reactive oxygen species (ROS)-induced granulosa cell (GC) apoptosis is regulated by a variety of signaling pathways involving numerous genes and transcription factors. In this study, we found expression of the p53-upregulated modulator of apoptosis (PUMA), a BH3-only Bcl-2 subfamily protein, in ovarian GCs during oxidative stress. By overexpression and knockdown of Forkhead box O1 (FoxO1), we found that FoxO1 regulates PUMA at the protein level. Moreover, as c-Jun N-terminal kinase (JNK) has been shown to activate FoxO1 by promoting its nuclear import, we used a JNK inhibitor to reduce FoxO1 activation and detected decreased PUMA messenger RNA expression and protein levels during oxidative stress. In addition, in vivo oxidative stress-induced upregulation of PUMA was found following injection of 3 nitropropionic acid in mice. In conclusion, oxidative stress increases PUMA expression regulated by FoxO1 in follicular GCs.