title: Role of oxidative stress in disrupting the function of negative glucocorticoid response element in daily amphetamine-treated rats.
abstract: Amphetamine (AMPH)-induced appetite suppression is associated with changes in hypothalamic reactive oxygen species (ROS), antioxidants, neuropeptides, and plasma glucocorticoid. This study explored whether ROS and glucocorticoid response element (GRE), which is the promoter site of corticotropin-releasing hormone (CRH) gene, participated in neuropeptides-mediated appetite control. Rats were treated daily with AMPH for four days, and changes in food intake, plasma glucocorticoid and expression levels of hypothalamic neuropeptide Y (NPY), proopiomelanocortin (POMC), superoxide dismutase (SOD), CRH, and glucocorticoid receptor (GR) were examined and compared. Results showed that food intake decreased and NPY gene down-regulated, while POMC, SOD, and CRH gene up-regulated during AMPH treatment. GR and GRE-DNA bindings were disrupted on Day 1 and Day 2 when glucocorticoid levels were still high. Pretreatment with GR inhibitor or ROS scavenger modulated mRNA levels in NPY, POMC, SOD and CRH in AMPH-treated rats. We suggest that disruptions of negative GRE (nGRE) on Day 1 and Day 2 are associated with an increase in oxidative stress during the regulation of NPY/POMC-mediated appetite control in AMPH-treated rats. These results advance the understanding of molecular mechanism in regulating AMPH-mediated appetite suppression.
authors.affiliation: Department of Food Science, Central Taiwan University of Science and Technology, Taichung City 406, Taiwan.
authors.forename: Shu-Chen
authors.initials: SC
authors.lastname: Chu
authors.affiliation: Department of Physiology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City 40201, Taiwan.
authors.forename: Ching-Han
authors.initials: CH
authors.lastname: Yu
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City 40201, Taiwan.
authors.forename: Pei-Ni
authors.initials: PN
authors.lastname: Chen
authors.affiliation: Institute of Biochemistry and Biotechnology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City 40201, Taiwan.
authors.forename: Yih-Shou
authors.initials: YS
authors.lastname: Hsieh
authors.affiliation: Department of Physiology, Chung Shan Medical University and Chung Shan Medical University Hospital, Taichung City 40201, Taiwan. Electronic address: dykuo@csmu.edu.tw.
authors.forename: Dong-Yih
authors.initials: DY
authors.lastname: Kuo
mesh_terms: D000661:Amphetamine / Q000009:adverse effects / Q000494:pharmacology*; D000818:Animals; D001067:Appetite Depressants / Q000494:pharmacology; D001923:Brain Chemistry / Q000187:drug effects; D003346:Corticotropin-Releasing Hormone / Q000187:drug effects / Q000378:metabolism; D004435:Eating / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000097:blood / Q000378:metabolism* / Q000502:physiology; D007031:Hypothalamus / Q000378:metabolism; D008297:Male; D009478:Neuropeptide Y / Q000378:metabolism; D018384:Oxidative Stress / Q000502:physiology; D011333:Pro-Opiomelanocortin / Q000378:metabolism; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011965:Receptors, Glucocorticoid / Q000187:drug effects; D020218:Response Elements; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: D001067:Appetite Depressants; D005938:Glucocorticoids; D009478:Neuropeptide Y; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D011333:Pro-Opiomelanocortin; D003346:Corticotropin-Releasing Hormone; D000661:Amphetamine; D013482:Superoxide Dismutase
keywords: Brain; Glucocorticoid response element; NPY; Oxidative stress; POMC