Expression of PUMA in follicular granulosa cells regulated by FoxO1 activation during oxidative stress

ZQ Liu, M Shen, WJ Wu, BJ Li, QN Weng… - Reproductive …, 2015 - journals.sagepub.com
ZQ Liu, M Shen, WJ Wu, BJ Li, QN Weng, M Li, HL Liu
Reproductive Sciences, 2015journals.sagepub.com
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 …
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.
Sage Journals