title: Enhancement of glucocorticoid receptor-mediated gene expression by cellular stress: evidence for the involvement of a heat shock-initiated factor or process during recovery from stress.
abstract: Recent reports have demonstrated the ability of cellular stress to cause a large increase in the maximal levels of steroid receptor-mediated gene expression, a process we refer to as the heat shock potentiation effect (HSPE). In the present work, we have analyzed the time of appearance of the HSPE on the glucocorticoid receptor (GR) of L929 cells stably-transfected with the MMTV-CAT reporter plasmid (LMCAT2 cells). In LMCAT2 cells exposed to heat shock (43 degrees C, 2-h) before addition of 1 microM dexamethasone, the first appearance of HSPE (CAT levels greater than hormone-alone) occurred at 8 h of recovery and continued to increase by 24 h of recovery. Treatment of LMCAT2 cells with 1 microM dexamethasone for 2 h before heat or chemical shock (sodium arsenite) resulted in the same delayed onset pattern for the HSPE. Based on a [35S]methionine assay and tests of L929 cells stably transfected with the constitutive pSV2-CAT reporter, evidence is provided that the delayed appearance of the HSPE is not due to the heat shock block of general protein synthesis or to specific repression of CAT mRNA expression or translation. By using short-term incubations (4 h) with dexamethasone during the recovery period, the peaks of HSPE expression during recovery were determined to be 12-16 h for CAT enzyme activities, and 4-8 h for CAT mRNA expression. Taken together, these results provide evidence that the timing of the HSPE is not dependent on the rate of GR activation, or on the type of stress, but rather on a factor or process that is either synthesized or activated during the recovery period following stress.
authors.affiliation: Department of Pharmacology, Medical College of Ohio, Toledo 43699, USA.
authors.forename: J L
authors.initials: JL
authors.lastname: Hu
authors.forename: X J
authors.initials: XJ
authors.lastname: Guan
authors.forename: E R
authors.initials: ER
authors.lastname: Sánchez
mesh_terms: D000818:Animals; D002460:Cell Line; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D017930:Genes, Reporter; D006360:Heat-Shock Proteins / Q000502:physiology*; D051379:Mice; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000235:genetics; D011965:Receptors, Glucocorticoid / Q000502:physiology*
chemical_list: D006360:Heat-Shock Proteins; D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D015500:Chloramphenicol O-Acetyltransferase