title: Expression of PUMA in Follicular Granulosa Cells Regulated by FoxO1 Activation During Oxidative Stress.
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.
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, PR China.
authors.forename: Ze-Qun
authors.initials: ZQ
authors.lastname: Liu
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, PR China.
authors.forename: Wang-Jun
authors.initials: WJ
authors.lastname: Wu
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, PR China.
authors.forename: Bo-Jiang
authors.initials: BJ
authors.lastname: Li
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, PR China.
authors.forename: Qian-Nan
authors.initials: QN
authors.lastname: Weng
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, PR China limei@njau.edu.cn.
authors.forename: Mei
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of Animal Genetics, Breeding and Reproduction, College of Animal Science and Technology, Nanjing Agricultural University, Nanjing, PR China liuhonglin@njau.edu.cn.
authors.forename: Hong-Lin
authors.initials: HL
authors.lastname: Liu
mesh_terms: D021581:Active Transport, Cell Nucleus; D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005496:Follicular Atresia / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D006107:Granulosa Cells / Q000187:drug effects / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051379:Mice; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D051017:Apoptosis Regulatory Proteins; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D016877:Oxidants; C488588:PUMA protein, mouse; D047428:Protein Kinase Inhibitors; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D048031:JNK Mitogen-Activated Protein Kinases
keywords: FoxO1; PUMA; apoptosis; follicular atresia; granulosa cell; oxidative stress