PMID- 23398290 OWN - NLM STAT- MEDLINE DCOM- 20130701 LR - 20211203 IS - 1471-4159 (Electronic) IS - 0022-3042 (Linking) VI - 125 IP - 4 DP - 2013 May TI - Retinoids and glucocorticoids target common genes in hippocampal HT22 cells. PG - 518-31 LID - 10.1111/jnc.12192 [doi] AB - Vitamin A metabolite retinoic acid (RA) plays a major role in the aging adult brain plasticity. Conversely, chronic excess of glucocorticoids (GC) elicits some deleterious effects in the hippocampus. We questioned here the involvement of RA and GC in the expression of target proteins in hippocampal neurons. We investigated proteins involved either in the signaling pathways [RA receptor beta (RARbeta) and glucocorticoid receptor (GR)] or in neuron differentiation and plasticity [tissue transglutaminase 2 (tTG) and brain-derived neurotrophic factor (BDNF)] in a hippocampal cell line, HT22. We applied RA and/or dexamethasone (Dex) as activators of the pathways and investigated mRNA and protein expression of their receptors and of tTG and BDNF as well as tTG activity and BDNF secretion. Our results confirm the involvement of RA- and GC-dependent pathways and their interaction in our neuronal cell model. First, both pathways regulate the transcription and expression of own and reciprocal receptors: RA and Dex increased RARbeta and decreased GR expressions. Second, Dex reduces the expression of tTG when associated with RA despite stimulating its expression when used alone. Importantly, when they are combined, RA counteracts the deleterious effect of glucocorticoids on BDNF regulation and thus may improve neuronal plasticity under stress conditions. In conclusion, GC and RA both interact through regulations of the two receptors, RARbeta and GR. Furthermore, they both act, synergistically or oppositely, on other target proteins critical for neuronal plasticity, tTG and BDNF. CI - (c) 2013 International Society for Neurochemistry. FAU - Brossaud, Julie AU - Brossaud J AD - INRA, Nutrition et Neurobiologie Integree, UMR1286, Bordeaux, France. FAU - Roumes, Helene AU - Roumes H FAU - Moisan, Marie-Pierre AU - Moisan MP FAU - Pallet, Veronique AU - Pallet V FAU - Redonnet, Anabelle AU - Redonnet A FAU - Corcuff, Jean-Benoit AU - Corcuff JB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130306 PL - England TA - J Neurochem JT - Journal of neurochemistry JID - 2985190R RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Glucocorticoids) RN - 0 (RNA, Messenger) RN - 0 (Receptors, Glucocorticoid) RN - 0 (Receptors, Retinoic Acid) RN - 0 (retinoic acid receptor beta) RN - 5688UTC01R (Tretinoin) RN - 7S5I7G3JQL (Dexamethasone) RN - EC 2.3.2.13 (Protein Glutamine gamma Glutamyltransferase 2) RN - EC 2.3.2.13 (Transglutaminases) RN - EC 3.6.1.- (GTP-Binding Proteins) SB - IM MH - Aging/physiology MH - Animals MH - Apoptosis/drug effects/physiology MH - Brain-Derived Neurotrophic Factor/genetics/metabolism MH - Cell Line, Transformed MH - Cell Survival/drug effects/physiology MH - Dexamethasone/metabolism/*pharmacology MH - Drug Synergism MH - GTP-Binding Proteins/genetics/metabolism MH - Gene Expression/drug effects/physiology MH - Glucocorticoids/metabolism/*pharmacology MH - Hippocampus/*cytology MH - Mice MH - Necrosis MH - Neural Stem Cells/cytology/*drug effects MH - Neuronal Plasticity/drug effects/physiology MH - Protein Glutamine gamma Glutamyltransferase 2 MH - RNA, Messenger/metabolism MH - Receptors, Glucocorticoid/genetics/metabolism MH - Receptors, Retinoic Acid/genetics/metabolism MH - Signal Transduction/*drug effects/physiology MH - Transglutaminases/genetics/metabolism MH - Tretinoin/metabolism/*pharmacology EDAT- 2013/02/13 06:00 MHDA- 2013/07/03 06:00 CRDT- 2013/02/13 06:00 PHST- 2012/11/15 00:00 [received] PHST- 2013/01/11 00:00 [revised] PHST- 2013/01/14 00:00 [accepted] PHST- 2013/02/13 06:00 [entrez] PHST- 2013/02/13 06:00 [pubmed] PHST- 2013/07/03 06:00 [medline] AID - 10.1111/jnc.12192 [doi] PST - ppublish SO - J Neurochem. 2013 May;125(4):518-31. doi: 10.1111/jnc.12192. Epub 2013 Mar 6.