title: p11 is up-regulated in the forebrain of stressed rats by glucocorticoid acting via two specific glucocorticoid response elements in the p11 promoter.
abstract: Posttraumatic stress disorder (PTSD) is one of the most common psychiatric disorders. Despite the extensive study of the neurobiological correlates of this disorder, the underlying mechanisms of PTSD are still poorly understood. Recently, a study demonstrated that dexamethasone (Dex), a synthetic glucocorticoid, can up-regulate p11, known as S100A10-protein which is down-regulated in patients with depression, (Yao et al., 1999; Huang et al., 2003) a common comorbid disorder in PTSD. These observations led to our hypothesis that traumatic stress may alter expression of p11 mediated through a glucocorticoid receptor. Here, we demonstrate that inescapable tail shock increased both prefrontal cortical p11 mRNA levels and plasma corticosterone levels in rats. We also found that Dex up-regulated p11 expression in SH-SY5Y cells through glucocorticoid response elements (GREs) within the p11 promoter. This response was attenuated by either RU486, a glucocorticoid receptor (GR) antagonist or mutating two of three glucocorticoid response elements (GRE2 and GRE3) in the p11 promoter. Finally, we showed that p11 mRNA levels were increased in postmortem prefrontal cortical tissue (area 46) of patients with PTSD. The data obtained from our work in a rat model of inescapable tail shock, a p11-transfected cell line and postmortem brain tissue from PTSD patients outline a possible mechanism by which p11 is regulated by glucocorticoids elevated by traumatic stress.
authors.affiliation: Center for the Study of Traumatic Stress, Department of Psychiatry, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. Lezhang@USUHS.mil
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: H
authors.initials: H
authors.lastname: Li
authors.forename: T P
authors.initials: TP
authors.lastname: Su
authors.forename: J L
authors.initials: JL
authors.lastname: Barker
authors.forename: D
authors.initials: D
authors.lastname: Maric
authors.forename: C S
authors.initials: CS
authors.lastname: Fullerton
authors.forename: M J
authors.initials: MJ
authors.lastname: Webster
authors.forename: C J
authors.initials: CJ
authors.lastname: Hough
authors.forename: X X
authors.initials: XX
authors.lastname: Li
authors.forename: R
authors.initials: R
authors.lastname: Ursano
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation / Q000379:methods; D003907:Dexamethasone / Q000494:pharmacology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004597:Electroshock / Q000009:adverse effects; D005938:Glucocorticoids / Q000494:pharmacology*; D006727:Hormone Antagonists / Q000494:pharmacology; D006801:Humans; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects*; D016548:Prosencephalon / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D009418:S100 Proteins / Q000235:genetics / Q000378:metabolism*; D013315:Stress, Psychological / Q000209:etiology / Q000473:pathology*; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects* / Q000502:physiology; D000099248:S100 Calcium Binding Protein A10
chemical_list: D017306:Annexin A2; D003907:Dexamethasone; D005938:Glucocorticoids; D006727:Hormone Antagonists; D015735:Mifepristone; D009687:Nuclear Proteins; D009418:S100 Proteins; D000099248:S100 Calcium Binding Protein A10