Corticotropin-releasing hormone stimulates SGK-1 kinase expression in cultured hippocampal neurons via CRH-R1

2008 ◽  
Vol 295 (4) ◽  
pp. E938-E946 ◽  
Author(s):  
Hui Sheng ◽  
Tingting Sun ◽  
Binhai Cong ◽  
Ping He ◽  
Yanmin Zhang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Protein Expression ◽  
Hippocampal Neurons ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Protein Levels ◽  
Mrna And Protein Expression ◽  
Inducible Protein ◽  
Kinase Expression ◽  
Cultured Hippocampal Neurons

Corticotropin-releasing hormone (CRH) has been shown to exhibit various functions in hippocampus. In the present study, we examined the effect of CRH on the expression of serum/glucocorticoid-inducible protein kinase-1 (SGK-1), a novel protein kinase, in primary cultured hippocampal neurons. A dose-dependent increase in mRNA and protein levels of SGK-1 as well as frequency of SGK-1-positive neurons occurred upon exposure to CRH (1 pmol/l to 10 nmol/l). These effects can be reversed by the specific CRH-R1 antagonist antalarmin but not by the CRH-R2 antagonist astressin 2B. Blocking adenylate cyclase (AC) activity with SQ22536 and PKA with H89 completely prevented CRH-induced mRNA and protein expression of SGK-1. Blockage of PLC or PKC did not block CRH-induced SGK-1 expression. Our results suggest that CRH act on CRH-R1 to stimulate SGK-1 mRNA and protein expression in cultured hippocampal neurons via a mechanism that is involved in AC/PKA signaling pathways.

Parathyroid hormone stimulates endothelial expression of atherosclerotic parameters through protein kinase pathways

2007 ◽  
Vol 292 (4) ◽  
pp. F1215-F1218 ◽  
Author(s):  
Gloria Rashid ◽  
Jacques Bernheim ◽  
Janice Green ◽  
Sydney Benchetrit
Keyword(s):  
Parathyroid Hormone ◽  
Protein Kinase ◽  
Protein Expression ◽  
Mrna Expression ◽  
Umbilical Vein ◽  
Protein Levels ◽  
Glycation End Products ◽  
Mrna And Protein Expression ◽  
Vascular Structures ◽  
The Impact

Parathyroid hormone (PTH), the major systemic calcium-regulating hormone, has been linked to uremic vascular changes. Considering the possible deleterious action of PTH on vascular structures, it seemed logical to evaluate the impact of PTH on the receptor of advanced glycation end products (RAGE) and interleukin 6 (IL-6) mRNA and protein expression, taking into account that such parameters might be involved in the pathogenesis of vascular calcification, atherosclerosis, and/or arteriolosclerosis. Human umbilical vein cord endothelial cells (HUVEC) were stimulated for 24 h with 10−12–10−10 mol/l PTH. The mRNA expression of RAGE and IL-6 was established by reverse transcriptase/PCR techniques. RAGE protein levels were determined by Western blot and IL-6 secretion was measured by ELISA. The pathways by which PTH may have an effect on HUVEC functions were evaluated. PTH (10−11–10−10mol/l) significantly increased RAGE mRNA and protein expression. PTH also significantly increased IL-6 mRNA expression without changes at protein levels. The addition of protein kinase (PKC or PKA) inhibitors or nitric oxide (NO) synthase inhibitors significantly reduced the RAGE and IL-6 mRNA expression and the RAGE protein expression. PTH stimulates the mRNA expressions of RAGE and IL-6 and the protein expression of RAGE. These stimulatory effects are probably through PKC and PKA pathways and are also NO dependent. Such data may explain the possible impact of PTH on the atherosclerotic and arteriosclerotic progression.

Corticotropin-releasing hormone activates connexin 43 via activator protein-1 transcription factor in human myometrial smooth muscle cells

2007 ◽  
Vol 293 (6) ◽  
pp. E1789-E1794 ◽  
Author(s):  
Xiang Wu ◽  
Hong Shen ◽  
Ling Yu ◽  
Mei Peng ◽  
Wei-Si Lai ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Protein Expression ◽  
Smooth Muscle Cells ◽  
Connexin 43 ◽  
Muscle Cells ◽  
Transient Transfection ◽  
Corticotropin Releasing Hormone ◽  
Cx43 Expression ◽  
Releasing Hormone ◽  
Mrna And Protein Expression

Corticotropin-releasing hormone (CRH) and connexin 43 (Cx43) play crucial roles in uterine contraction and the onset of labor. The aim of the present study was to investigate the regulatory effects of CRH on Cx43 expression in human myometrial smooth muscle cells (SMCs) and, potentially, its activation of the c-Fos/activator protein (AP)-1 signaling pathway. Human myometrial SMCs collected from nonpregnant women were treated with different concentrations of CRH. Transient transfection of AP-1 decoy oligodeoxynucleotide (ODN) was used to block AP-1 sites of Cx43. The transcriptional activity of AP-1 was detected by luciferase assay. Cx43 protein expression was visualized by immunofluorescence staining. mRNA and protein expression of c-Fos and Cx43 were demonstrated by real-time quantitative RT-PCR and Western blot, respectively. CRH facilitated Cx43 expression and enhanced AP-1 promoter activity in human uterine SMCs. After CRH treatment, Cx43 expression in the cytoplasm increased significantly. CRH significantly increased mRNA and protein expression of c-Fos and Cx43 in a dose-dependent manner ( P < 0.01). A transient transfection of AP-1 decoy ODN did not affect CRH regulation of c-Fos ( P > 0.05) but almost completely abolished CRH-induced enhancement of Cx43 expression ( P < 0.01). In human primary myometrial SMCs, CRH enhances Cx43 mRNA and protein expression through upregulation of c-Fos expression. Blockade of AP-1 sites to the Cx43 promoter can neutralize the CRH-induced upregulation of Cx43.

GCM2 Silencing in Parathyroid Adenoma is associated with Promoter Hypermethylation and Gain of Methylation on Histone 3

2021 ◽  
Author(s):  
Priyanka Singh ◽  
Sanjay Kumar Bhadada ◽  
Divya Dahiya ◽  
Uma Nahar Saikia ◽  
Ashutosh Kumar Arya ◽  
...  
Keyword(s):  
Protein Expression ◽  
Parathyroid Adenoma ◽  
Dna Methyltransferase ◽  
Promoter Hypermethylation ◽  
Epigenetic Alterations ◽  
Protein Levels ◽  
Histone 3 ◽  
Parathyroid Adenomas ◽  
Mrna And Protein Expression

Abstract Purpose Glial cells missing 2 (GCM2), a zinc finger-transcription factor, is essentially required for the development of parathyroid glands. We sought to identify if the epigenetic alterations in the GCM2 transcription are involved in the pathogenesis of sporadic parathyroid adenoma. In addition, we examined the association between promoter methylation and histone modifications with disease indices. Experimental design mRNA and protein expression of GCM2 were analyzed by RT-qPCR and immunohistochemistry in 33 adenomatous and 10 control parathyroid tissues. DNA methylation and histone methylation/acetylation of GCM2 promoter were measured by bisulfite sequencing and ChIP-qPCR. Additionally, we investigated the role of epigenetic modifications on GCM2 and DNA methyltransferase 1 (DNMT1) expression in PTH-C1 cells by treating with 5-aza 2’deoxycytidine (DAC) and BRD4770 and assessed for GCM2 mRNA and DNMT1 protein levels. Results mRNA and protein expression of GCM2 were lower in sporadic adenomatous than in control parathyroid tissues. This reduction correlated with hypermethylation (P&lt;0.001) and higher H3K9me3 levels in GCM2 promoter (P&lt;0.04) in adenomas. In PTH-C1 cells, DAC treatment resulted in increased GCM2 transcription and decreased DNMT1 protein expression, while cells treated with the BRD4770 showed reduced H3K9me3 levels but a non-significant change in GCM2 transcription. Conclusion These findings suggest the concurrent association of promoter hypermethylation and higher H3K9me3 with the repression of GCM2 expression in parathyroid adenomas. Treatment with DAC restored GCM2 expression in PTH-C1 cells. Our results showed a possible epigenetic landscape in the tumorigenesis of parathyroid adenoma and also that DAC may be promising avenues of research for parathyroid adenoma therapeutics.

PTH regulates expression of ClC-5 chloride channel in the kidney

2000 ◽  
Vol 278 (2) ◽  
pp. F238-F245 ◽  
Author(s):  
Ian V. Silva ◽  
Carol J. Blaisdell ◽  
Sandra E. Guggino ◽  
William B. Guggino
Keyword(s):  
Vitamin D ◽  
Protein Expression ◽  
Chloride Channel ◽  
Urinary Calcium ◽  
Kidney Cortex ◽  
Lower Serum ◽  
Protein Levels ◽  
Calcium Reabsorption ◽  
Mrna And Protein Expression ◽  
Serum Pth

Mutations in the chloride channel, ClC-5, have been described in several inherited diseases that result in the formation of kidney stones. To determine whether ClC-5 is also involved in calcium homeostasis, we investigated whether ClC-5 mRNA and protein expression are modulated in rats deficient in 1α,25(OH)2 vitamin D3 with and without thyroparathyroidectomy. Parathyroid hormone (PTH) was replaced in some animals. Vitamin D-deficient, thyroparathyrodectomized rats had lower serum and higher urinary calcium concentrations compared with control animals as well as lower serum PTH and calcitonin concentrations. ClC-5 mRNA and protein levels in the cortex decrease in vitamin D-deficient, thyroparathyroidectomized rats compared with both control and vitamin D-deficient animals. ClC-5 mRNA and protein expression increase near to control levels in vitamin D-deficient, thyroparathyroidectomized rats injected with PTH. No significant changes in ClC-5 mRNA and protein expression in the medulla were detected in any experimental group. Our results suggest that PTH modulates the expression of ClC-5 in the kidney cortex and that neither 1α,25(OH)2 vitamin D3 nor PTH regulates ClC-5 expression in the medulla. The pattern of expression of ClC-5 varies with urinary calcium. Animals with higher urinary calcium concentrations have lower levels of ClC-5 mRNA and protein expression, suggesting that the ClC-5 chloride channel plays a role in calcium reabsorption.

Corticotropin-releasing hormone acts on guinea pig ileal smooth muscle via protein kinase A

1999 ◽  
Vol 438 (2) ◽  
pp. 205-212 ◽  
Author(s):  
D. B. Duridanova ◽  
P. S. Petkova-Kirova ◽  
L. T. Lubomirov ◽  
H. Gagov ◽  
K. Boev
Keyword(s):  
Smooth Muscle ◽  
Protein Kinase ◽  
Guinea Pig ◽  
Protein Kinase A ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Kinase A

scholarly journals Discrepancy between Jun/Fos Proto-Oncogene mRNA and Protein Expression in the Rheumatoid Arthritis Synovial Membrane

J ◽  
2020 ◽  
Vol 3 (2) ◽  
pp. 181-194 ◽  
Author(s):  
René Huber ◽  
Bruno Stuhlmüller ◽  
Elke Kunisch ◽  
Raimund W. Kinne
Keyword(s):  
Rheumatoid Arthritis ◽  
Protein Expression ◽  
Synovial Membrane ◽  
Rna Binding ◽  
Mrna Level ◽  
Joint Disease ◽  
Protein Levels ◽  
Modifying Factors ◽  
Mrna And Protein Expression ◽  
Joint Trauma

Rheumatoid arthritis (RA) is a chronic inflammatory and destructive joint disease characterized by overexpression of pro-inflammatory/pro-destructive mediators, whose regulation has been the focus of our previous studies. Since the expression of these proteins commonly depends on AP-1, the expression of the AP-1-forming subunits cJun, JunB, JunD, and cFos was assessed in synovial membrane (SM) samples of RA, osteoarthritis (OA), joint trauma (JT), and normal controls (NC) using ELISA and qRT-PCR. With respect to an observed discrepancy between mRNA and protein levels, the expression of the mRNA stability-modifying factors AU-rich element RNA-binding protein (AUF)-1, tristetraprolin (TTP), and human antigen R (HuR) was measured. JunB and JunD protein expression was significantly higher in RA-SM compared to OA and/or NC. By contrast, jun/fos mRNA expression was significantly (cjun) or numerically decreased (junB, junD, cfos) in RA and OA compared to JT and/or NC. Remarkably, TTP and HuR were also affected by discrepancies between their mRNA and protein levels, since they were significantly decreased at the mRNA level in RA versus NC, but significantly or numerically increased at the protein level when compared to JT and NC. Discrepancies between the mRNA and protein expression for Jun/Fos and TTP/HuR suggest broad alterations of post-transcriptional processes in the RA-SM. In this context, increased levels of mRNA-destabilizing TTP may contribute to the low levels of jun/fos and ttp/hur mRNA, whereas abundant mRNA-stabilizing HuR may augment translation of the remaining mRNA into protein with potential consequences for the composition of the resulting AP-1 complexes and the expression of AP-1-dependent genes in RA.

scholarly journals Corticotropin-releasing hormone (CRH) alters mitochondrial morphology and function by activating the NF-kB-DRP1 axis in hippocampal neurons

2020 ◽  
Vol 11 (11) ◽  
Author(s):  
Chiara R. Battaglia ◽  
Silvia Cursano ◽  
Enrico Calzia ◽  
Alberto Catanese ◽  
Tobias M. Boeckers
Keyword(s):  
Hippocampal Neurons ◽  
Morphological Changes ◽  
Mitochondrial Dynamics ◽  
Synaptic Activity ◽  
Mitochondrial Activity ◽  
Mitochondrial Morphology ◽  
Significant Shift ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone

AbstractNeuronal stress-adaptation combines multiple molecular responses. We have previously reported that thorax trauma induces a transient loss of hippocampal excitatory synapses mediated by the local release of the stress-related hormone corticotropin-releasing hormone (CRH). Since a physiological synaptic activity relies also on mitochondrial functionality, we investigated the direct involvement of mitochondria in the (mal)-adaptive changes induced by the activation of neuronal CRH receptors 1 (CRHR1). We observed, in vivo and in vitro, a significant shift of mitochondrial dynamics towards fission, which correlated with increased swollen mitochondria and aberrant cristae. These morphological changes, which are associated with increased NF-kB activity and nitric oxide concentrations, correlated with a pronounced reduction of mitochondrial activity. However, ATP availability was unaltered, suggesting that neurons maintain a physiological energy metabolism to preserve them from apoptosis under CRH exposure. Our findings demonstrate that stress-induced CRHR1 activation leads to strong, but reversible, modifications of mitochondrial dynamics and morphology. These alterations are accompanied by bioenergetic defects and the reduction of neuronal activity, which are linked to increased intracellular oxidative stress, and to the activation of the NF-kB/c-Abl/DRP1 axis.

Corticotropin-releasing hormone activates protein kinase C in an isoenzyme-specific manner

2005 ◽  
Vol 327 (3) ◽  
pp. 828-836 ◽  
Author(s):  
Erini Dermitzaki ◽  
Christos Tsatsanis ◽  
Ioannis Charalampopoulos ◽  
Ariadne Androulidaki ◽  
Vassiliki-Ismini Alexaki ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Kinase C ◽  
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