OBJECTIVES: CREB (c-AMP response element binding protein) is known as a key mediator of the therapeutic response to antidepressants. We investigated the change of CREB-phosphorylation (pCREB) at the early point of the fluoxetine treatment to find out it can be a predictor for antidepressant response. METHODS: We evaluated the pCREB of T - lymphocyte nuclear extracts from 18 depressed patients at 0 and 1th week during fluoxetine treatment (20 mg/day). Responders were defined as the > or = 50% reduction of HAM-D score in 4 weeks. We compared the changes of pCREB at 0 and 1th week between responders and non-responders. RESULTS: The responders showed a significant increase of pCREB at week 1 compared with week 0. The HAM-D difference between week 0 and 4 was positively correlated with the change of pCREB response. CONCLUSION: These results suggest that the early change of pCREB in peripheral lymphocyte can predict the later response of antidepressant. The correlation showed pCREB directly reflects a response status to the antidepressant fluoxetine and clinical improvement.
Antidepressive Agents ; Depression ; Fluoxetine ; Humans ; Lymphocytes ; Response Elements

OBJECTIVES: CREB (c-AMP response element binding protein) is known as a key mediator of the therapeutic response to antidepressants. We investigated the change of CREB-phosphorylation (pCREB) at the early point of the fluoxetine treatment to find out it can be a predictor for antidepressant response. METHODS: We evaluated the pCREB of T - lymphocyte nuclear extracts from 18 depressed patients at 0 and 1th week during fluoxetine treatment (20 mg/day). Responders were defined as the > or = 50% reduction of HAM-D score in 4 weeks. We compared the changes of pCREB at 0 and 1th week between responders and non-responders. RESULTS: The responders showed a significant increase of pCREB at week 1 compared with week 0. The HAM-D difference between week 0 and 4 was positively correlated with the change of pCREB response. CONCLUSION: These results suggest that the early change of pCREB in peripheral lymphocyte can predict the later response of antidepressant. The correlation showed pCREB directly reflects a response status to the antidepressant fluoxetine and clinical improvement.
Antidepressive Agents ; Depression ; Fluoxetine ; Humans ; Lymphocytes ; Response Elements

Estrogen is a steroid hormone produced mainly by the ovaries. It combines with the nuclear receptors to exert the biological effects influencing the metabolism of body. Elevated levels of estrogen are often associated with altered iron levels in mammals. Furthermore, the findings of estrogen response element (ERE) have demonstrated that estrogen affects iron metabolism directly in peripheral tissues. In this review, we will briefly summarize the effect of estrogen on iron metabolism in mammals, and discuss recent progress in the mechanisms of estrogen on some iron related proteins in order to provide guidance for clinical use of estrogen. Estrogen and iron metabolism are closely related, but the exact regulatory mechanisms still need further exploration.
Animals ; Estrogens ; metabolism ; Humans ; Iron ; metabolism ; Mammals ; Response Elements

BACKGROUND: Surfactant proteins are important in the regulation of the surfactant secretion, synthesis and recycling. Glucocorticoids are known to have primary or secondary effects on gene expression and can alter the rate of gene transcription. The hydrophilic and hydrophobic surfactant protein have been shown to be upregulated by glucocorticoids in vitro but its regulation in vivo, however, is not well established. The authors carried out nuclear run on assays to determine wheather glucocorticoids altered the transcription rate of SP-A, SP-B and SP-C genes. METHODS: Adult rats were given the 2 mg/kg dose of subcutaneous dexamethasone for 2 days and sacrified at 2 days. The transcription rate of SP-A, SP-B and SP-C genes were measured by nuclear run on assays. RESULTS: Treatment with 2 mg/kg dexamethasone increased transcription of SP-A gene (1.6-fold) and SP-C gene (1.3-fold) compared to the control for SP-A and SP-C after 2 days, which were not statistically significant. The rate of gene transcription for SP-B at 2 days after 2 mg/kg dexamethasone administration was significantly increased by 5.3-fold compared to the control for SP-B (p<0.005). The rates of gene transcription for hydrophilic and hydrophobic surfactant proteins, even in the hydrophobic surfactant proteins SP-B and SP-C were different. CONCLUSIONS: The authors conclude that the difference in dexamethasone sensitivity may indicate that the three surfactant protein genes contain glucocorticoid response elements with different affinities for receptor in vivo.
Adult ; Animals ; Dexamethasone ; Gene Expression ; Glucocorticoids ; Humans ; Pulmonary Surfactants ; Rats ; Recycling ; Response Elements

OBJECTIVE: The aims of the present study were to explore the behavioural effects and to understand the possible mode of action of Bacopa monnieri extract (BME) on chronic unpredictable stress (CUS) induced depressive model and the biochemical alterations such as brain derived neurotrophic factor (BDNF), Akt, cyclic-AMP response element binding (CREB) protein level in the hippocampus of rats. METHODS: We examined the effects of chronic administration of BME on CUS exposed rats for 28 days. Behavioural changes were assessed by sucrose consumption and open field test to assess the effect of BME on CUS-induced depression. The mechanisms underlying antidepressant like action of BME was further evaluated by measuring levels of BDNF, Akt, and CREB in the hippocampus of rat brain and compared with the standard tricyclic antidepressant drug imipramine (20 mg/kg body weight). RESULTS: Exposure to CUS for 28 days produced depression-like behavior in rats, as indicated by significant decreases in sucrose consumption, locomotor activity including decreased BDNF, Akt and CREB levels in the hippocampus. Daily administration of BME at a dose of (80 mg/kg body weight) significantly reverses the behavioral alteration and restored the normal level of BDNF, total and phospho-Akt, total and phospho CREB in the hippocampus of CUS induced rats as compared to vehicle treated control rats. CONCLUSION: These findings suggest that BME ameliorates CUS induced behavioural depression in rats and that can be used as a potent therapeutic agent in treating depressive like behavior.
Animals ; Bacopa* ; Brain ; Brain-Derived Neurotrophic Factor* ; Depression ; Hippocampus* ; Imipramine ; Motor Activity ; Rats* ; Response Elements ; Sucrose

The aim of the present work is to investigate the existence of epistatic interactions possibly influencing psychotropic agents' response between rs6740584 within Cyclic adenosine monophosphate Response Element Binding (CREB) and rs12775799 within cAMP response element-modulator (CREM) variants in bipolar disorder (BD) and major depressive disorder (MDD). All BD and MDD patients were administered with the Young Mania Rating Scale (YMRS) and Hamilton Depression Rating Scale (HAMD) at baseline and at endpoint, respectively. A multiple regression model was employed to investigate the existence of possible epistatic interactions between the two variants and diverse clinical factors including drug response in affective disorders. No significant epistatic interaction was observed between rs6740584 within CREB and rs12775799 within CREM on both symptom improvement and other clinical factors in affective disorders. Our preliminary results suggest that no epistatic interaction between rs6740584 within CREB and rs12775799 within CREM should exist on clinical improvement and clinical factors in affective disorders.
Adenosine Monophosphate ; Bipolar Disorder ; Depression ; Depressive Disorder, Major ; Humans ; Mood Disorders* ; Response Elements

The cytoprotective enzyme heme oxygenase-1 (HO-1) influences endothelial cell survival, proliferation, inflammatory response, and angiogenesis in response to various angiogenic stimuli. In this study, we investigate the involvement of HO-1 in the angiogenic activity of orexin-A. We showed that orexin-A stimulates expression and activity of HO-1 in human umbilical vein endothelial cells (HUVECs). Furthermore, we showed that inhibition of HO-1 by tin (Sn) protoporphryin-IX (SnPP) reduced orexin-A-induced angiogenesis in vivo and ex vivo. Orexin-A-stimulated endothelial tube formation and chemotactic activity were also blocked in SnPP-treated vascular endothelial cells. Orexin-A treatment increased the expression of nuclear factor erythroid-derived 2 related factor 2 (Nrf2), and antioxidant response element (ARE) luciferase activity, leading to induction of HO-1. Collectively, these findings indicate that HO-1 plays a role as an important mediator of orexin-A-induced angiogenesis, and provide new possibilities for therapeutic approaches in pathophysiological conditions associated with angiogenesis.
Antioxidant Response Elements ; Endothelial Cells* ; Heme Oxygenase-1* ; Human Umbilical Vein Endothelial Cells ; Luciferases ; Tin ; Orexins

It is noted that chalcone derivatives have characteristic diverse pharmacological properties, and that precise evidence has been growing that they could regulate a tumor necrosis factor-α (TNF-α) induced insulin resistance. The purpose of the present investigation is to elucidate the effects of the identified chalcone derivatives on adipogenesis, and to find the underlying mechanism of action in that case. Consequently, we first investigated whether the chalcone derivatives could affect the identified PPARγ-induced transcriptional activity on the proliferator-activated receptor response elements (PPRE) at target promoters, and find that trans-chalcone most significantly increased the PPARγ-induced transcriptional activity. Additionally, we confirmed that there were up-regulatory effects of trans-chalcone during the adipogenesis and lipid accumulation, and on the mRNA of adipogenic factors in 3T3-L1 cells. Next, we examined the effect of trans-chalcone on the inhibition induced by TNF-α on adipogenesis. To that end, we noted that the treatment with trans-chalcone attenuated the effect of TNF-α mediated secretion of various adipokines that are involved in insulin sensitivity. For this reason, we noted that this study clearly demonstrates that trans-chalcone enhanced adipogenesis, in part, by its potent effect on PPARγ activation and by its reverse effect on TNF-α.
3T3-L1 Cells ; Adipogenesis ; Adipokines ; Chalcone ; Insulin Resistance ; Necrosis ; Response Elements ; RNA, Messenger

OBJECTIVE: The molecules related with the intracellular signal transduction system are one of the main targets for the mode of mechanisms of antidepressant treatment in depressive patients. In vivo and in vitro studies have provided the evidence that the transcription factor, CREB (c-AMP response element binding protein) is the key mediator of the therapeutic response to antidepressants. We investigated the relationship between the treatment response to fluoxetine for 6 weeks and the change of CREB immunoreactivity in peripheral T lymphocyte. METHODS: CREB-expression and phosphorylation were quantified via western blot, and binding activity between transcription factor and CRE-oligonucleotide via electrophoretic mobility shift assay (EMSA) in nuclear extracts from 14 normal controls and 31 depressed patients at 0 and 6th week during fluoxetine treatment (20 mg/day). Responder was defined as the > or =50% of reduction or < or =7 of HAM-D score. We compared the changes of CREB during 6 weeks of fluoxetine treatment between drug responders and non-responders using SPSS11.0. RESULTS: After six weeks of treatment with fluoxetine, the drug responders showed a significant increase in CREB (p=0.024 by t-test) and p-CREB (p=0.045 by Mann-Whitney U test) compared with the non-responders. The change of CREB immunoreactivity was positively correlated with the change of p-CREB (r=0.770, p=0.000 by Spearman's rho), and the change of p-CREB was also positively correlated with CRE-DNA binding (r=0.753, p=0.000 by Spearman's rho). CONCLUSION: These results suggest that CREB response in peripheral lymphocyte may reflect and mediate the response to antidepressant treatment in depressed patients.
Antidepressive Agents ; Blotting, Western ; Depression ; Electrophoretic Mobility Shift Assay ; Fluoxetine ; Humans ; Lymphocytes* ; Phosphorylation ; Response Elements ; Signal Transduction ; Transcription Factors

In-vitro assay methods were established to evaluate transactivation and binding activity of compounds on peroxisome proliferator-activated receptor y (PPARγ). Firstly, plasmids were constructed for transactivation assay of PPARγ response element (PPRE) triggered reporter gene expression, and for cell-based binding activity assay of the chimeric receptor, which was fused with PPARγ ligand binding domain (LBD) and yeast transcriptional activator Gal4. Secondly, by using PPARy competitive binding assay based on time resolved-fluorescence resonance energy transfer (TR-FRET), affinities of compounds and drugs to PPARγ were evaluated. In application of these above methods, the PPARγ activating potency and characteristics of different compounds were evaluated, and a novel benzeneselfonamide derivative, ZLJ01, was found to have comparable binding activity and affinity with the well-known PPARy agonist, but lack of PPRE mediated transactivation activity. In preliminary study on in-vitro hypoglycemic activity, ZLJ1 was found to promote insulin-stimulated glucose uptake by liver cells. Therefore, we believe that combining transactivation and binding activity as well as affinity evaluation, the system could be used to screen non-agonist PPARγ ligand as anovel PPARγ modulator
Genes, Reporter ; Hepatocytes ; Hypoglycemic Agents ; chemistry ; Ligands ; PPAR gamma ; agonists ; chemistry ; Plasmids ; Response Elements ; Sulfonamides ; chemistry ; Transcriptional Activation