Abstract 340: Psychological Stress Impairs Both Endothelial Function and Insulin Sensitivity via Activation of Inflammation and ER Stress Pathways Mediated by Corticotropin-Releasing Hormone

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Ick-Mo Chung ◽  
Hee Young Kim ◽  
Youn Jung Lee
Keyword(s):  
Insulin Sensitivity ◽  
Endothelial Function ◽  
Er Stress ◽  
Psychological Stress ◽  
Underlying Mechanism ◽  
Control Group ◽  
No Production ◽  
Nuclear Fraction ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone

Background: Psychological stress may contribute to atherogenesis, although the underlying mechanism is poorly understood yet. We studied the role of corticotropin-releasing hormone (CRH) in the pathogenesis of stress-induced endothelial dysfunction and insulin resistance with specific focus on inflammation and ER stress pathways. Methods and Results: Immobilization stress (IS) was applied (2 hr/d) for 14 d to male 8-wk OLETF rats, whereas control groups comprised of rats without IS (n≥7 for each). 14d-IS decreased acetylcholine (Ach)-induced NO production, measured by direct NO electrochemical microsensor, from the aorta along with decreased expression of eNOS mRNA compared with control group. 14d-IS did not significantly change plasma glucose, but increased plasma insulin (342.5±6.3 vs. 496.0±51.6 pg/ml, p<0.05) and HOMA-IR (3.1±0.2 vs.4.7±0.5 mmol/LxμIU/mL, p<0.05) compared with control group. IS increased phosphorylation of both IRS1 serine and ERK, and increased expression of ER stress marker BiP. IS also increased translocation of NF-kB subunit p65 into nucleal fraction, and increased mRNA expression of both TNF-α and MCP-1 in the liver. Real-time RT-qPCR study showed that 1d IS increased expression of CRH mRNA and urocortin 2 mRNA in the hypothalamus by 2.5 folds and expression of CRH receptor type 2 mRNA in the aorta by 7.8 folds compared with control group. In cultured monocyte U937 cells, CRH induced translocation of NF-kB subunit p65 into nuclear fraction, and increased expression of BiP, phosphorylated inositol requiring enzyme 1, and MCP-1 mRNA. In cultured HUVECs, CRH pretreatment inhibited insulin-stimulated eNOS phosphorylation at Ser 1177 . Conclusions: Psychological stress impairs both endothelial function and insulin sensitivity probably via activation of NF-kB-mediated inflammation and ER stress pathways by CRH.

Association between genetic variant rs2267716 of CRHR2 gene with colorectal cancer

2021 ◽  
pp. jim-2021-002047
Author(s):  
Angélica Araceli Ramírez-Guerrero ◽  
Christian Octavio González-Villaseñor ◽  
Evelia Leal-Ugarte ◽  
Melva Gutiérrez-Angulo ◽  
Mario Ramírez-Flores ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Angiogenesis Inhibitor ◽  
Cross Sectional Study ◽  
Control Group ◽  
Corticotropin Releasing Hormone ◽  
Allelic Discrimination Assay ◽  
Allelic Discrimination ◽  
Cross Sectional ◽  
Releasing Hormone ◽  
Significant Difference

Colorectal cancer (CRC) is the third most common cancer and one of the main causes of death around the world. Multiple lines of evidence have suggested the role of the corticotropin-releasing hormone (CRH) family in CRC induction, including the low expression of corticotropin-releasing hormone receptor 2 (CRHR2), which is an angiogenesis inhibitor and inflammatory modulator. Previous research suggests that CRHR2 expression in colonic intestinal cells can regulate migration, proliferation and apoptosis through the modulation of several pathways. The aim of this study was to analyze the association of the rs10250835, rs2267716 and rs2267717 variants of CRHR2 gene with CRC in the Mexican population in order to consider its predictive value in CRC. This cross-sectional study included a group of 187 unrelated patients with sporadic CRC and a control group of 191 healthy blood donors. DNA extraction from peripheral blood was carried out using the Miller method. Identification of the rs10250835 variant was performed using PCR-restriction fragment length polymorphism (RFLP) and the rs2267716 and rs2267717 variants using TaqMan allelic discrimination assay. The minor allele homozygous CC of the rs2267716 variant of CRHR2 showed significant difference between CRC and control group (p=0.025), as well as the GCA haplotype (p=0.007), corresponding to the rs10250835, rs2267716 and rs2267717 variants, respectively. Our results suggest that the rs2267716 variant and GCA haplotype of CRHR2 represent a risk factor for CRC development in Mexican patients.

scholarly journals Rejuvenated Circulating Endothelial Progenitor Cells and Nitric Oxide in Premenopausal Women with Hyperhomocysteinemia

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Long Peng ◽  
Qianlin Gu ◽  
Zhenhua Huang ◽  
Lijin Zeng ◽  
Chang Chu ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Function ◽  
Progenitor Cells ◽  
Endothelial Progenitor Cells ◽  
Premenopausal Women ◽  
Underlying Mechanism ◽  
No Production ◽  
Endothelial Progenitor ◽  
Repair Capacity ◽  
Circulating Endothelial Progenitor Cells

Hyperhomocysteinemia (HHcy) induced endothelial dysfunction is associated with disturbance in circulating endothelial progenitor cells (EPCs). Nevertheless, whether this unfavorable effect of HHcy on circulating EPCs also exists in premenopausal women is still unknown. Therefore, this leaves an area for the investigation of the difference on the number and activity of circulating EPCs in premenopausal women with hyperhomocysteinemia and its underlying mechanism. The number of circulating EPCs was measured by fluorescence-activated cell sorter analysis, as well as DiI-acLDL and lectin fluorescent staining. The migration and proliferation of circulating were evaluated by the Transwell chamber assay and MTT. Additionally, the endothelial function and levels of nitric oxide (NO), VEGF, and GM-CSF in plasma and culture medium were determined. The number or activity of circulating EPCs and flow-mediated dilatation (FMD) in premenopausal women with or without HHcy were higher than those in postmenopausal women. However, no significant effect of HHcy on the number or activity of circulating EPCs in premenopausal women was observed. A similar alteration in NO level between the four groups was observed. There was a correlation between FMD and the number or activity of EPCs, as well as NO level in plasma or secretion by EPCs. For the first time, our findings illuminated the quantitive or qualitative alterations of circulating EPCs and endothelial function in premenopausal patients with HHcy are preserved, which was associated with retained NO production. The recuperated endothelial repair capacity is possibly the potential mechanism interpreting cardiovascular protection in premenopausal women with HHcy.

Neuropeptide Y reverses corticotropin-releasing hormone- and psychological stress-caused shortening of sodium pentobarbital-induced sleep in rats

1996 ◽  
Vol 725 (2) ◽  
pp. 272-275 ◽  
Author(s):  
Konagi Yamada ◽  
Tamotsu Shibasaki ◽  
Chiaki Tsumori ◽  
Toshihiro Imaki ◽  
Marl Hotta ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Psychological Stress ◽  
Sodium Pentobarbital ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone

scholarly journals Sex-Dependent Association of DNA Methylation in the Coding Region of the Corticotropin-Releasing Hormone Gene and Schizophrenia

2021 ◽  
Author(s):  
Lili Qing ◽  
Peng Xiong ◽  
Yumei Lu ◽  
Hongyan Jiang ◽  
Shengjie Nie
Keyword(s):  
Hpa Axis ◽  
Peripheral Blood ◽  
Mental Disease ◽  
Methylation Status ◽  
Underlying Mechanism ◽  
Corticotropin Releasing Hormone ◽  
Coding Region ◽  
Releasing Hormone ◽  
Chronic Disability ◽  
Schizophrenic Patients

Abstract Schizophrenia (SCZ) is a common mental disease causing severe chronic disability. Epigenetic changes in HPA axis-related genes are considered to play an important role in SCZ pathogenesis. Unfortunately, the methylation status of the corticotropin-releasing hormone ( CRH ) gene, which is the central driving force in the HPA axis, has not been reported in SCZ patients. Here, we used the sodium bisulfite and MethylTarget methods to detect the DNA methylation status of the CRH gene coding region in peripheral blood samples from 70 schizophrenic patients and 68 healthy controls. The results showed that the methylation level of the CRH gene CDS was significantly increased in SCZ patients, especially in the male subgroup. In conclusion, this study showed that differences in CRH gene CDS methylation were detectable in the peripheral blood of SCZ patients and that epigenetic abnormalities in the CRH gene were closely related to SCZ, revealing that epigenetic processes may mediate the pathophysiology of SCZ. Further research should address the underlying mechanism whereby CRH gene methylation regulates the occurrence and development of SCZ.

Abstract 188: Immobilization Stress Exacerbates Insulin Resistance and Endothelial Dysfunction via Inhibition of Insulin-Stimulated eNOS Activation and via Enhancement of NF-kB Activation by Corticotropin-Releasing Hormone

2013 ◽  
Vol 33 (suppl_1) ◽  
Author(s):  
Ick-Mo Chung ◽  
Hee Young Kim ◽  
Youn Jung Lee ◽  
Kuy-Sook Lee ◽  
Mi-Kyung Shin
Keyword(s):  
Insulin Resistance ◽  
Endothelial Dysfunction ◽  
Immobilization Stress ◽  
Nuclear Fraction ◽  
Corticotropin Releasing Hormone ◽  
Control Groups ◽  
Releasing Hormone ◽  
Oletf Rats ◽  
Erk Phosphorylation ◽  
Huvec Cells

Objectives Psychological stress may contribute to the development of atherosclerosis and insulin resistance. However, its mechanism is poorly understood. We studied if stress induces insulin resistance and endothelial dysfunction, and assessed the role of stress-associated corticotropin-releasing hormone (CRH) in inflammation and insulin signaling pathways. Methods and Results Immobilization stress (IS) was applied (2 hr/d) for 14 d to male 8-wk (YI2O: before DM phenotype) and 21-wk (EI2O: DM phenotype) OLETF rats, whereas control groups comprised of rats without IS with same age (YCO and ECO, respectively; n=7~10 for each group). Systolic blood pressure was significantly increased after 14d-IS in YI2O and EI2O, whereas it was not changed in control groups. Acetylcholine-induced, but not nitroprusside-induced, vasorelaxation, measured in superior mesenteric artery, was significantly decreased by 14d IS compared with each control groups, suggesting that IS induced endothelial dysfunction. 14d-IS increased plasma insulin (342.5±6.3 vs 496±51.6 pg/ml) and HOMA-IR (3.1±0.2 vs 4.7±0.5 mmol/LxμIU/mL) in 8-wk OLETF rats (control vs stress, all p <0.05). Western blot analysis using thoracic aorta showed 14d-IS increased expression of Rho-associated kinase-1 and p22 phox subunit of NAD(P)H oxidase compared with control groups. eNOS phosphorylation at Ser 1177 was increased by treatment with insulin (2nM) in cultured HUVEC cells, but this was blocked by pretreatment with CRH (100 nM). On the contrary, an increase in ERK phosphorylation by insulin treatment was further enhanced by CRH pretreatment in HUVEC cells. CRH also induced translocation of NF-kB subunit p65 into nuclear fraction in monocyte cell line U937 cells. Conclusions Immobilization stress exacerbates insulin resistance and endothelial dysfunction in a prediabetic animal model at least partly via inhibition of insulin-mediated eNOS activation and via enhancement of inflammation through ERK pathway and NF-kB activation by CRH.

Psychological stress and corticotropin-releasing hormone increase intestinal permeability in humans by a mast cell-dependent mechanism

Gut ◽  
2013 ◽  
Vol 63 (8) ◽  
pp. 1293-1299 ◽  
Author(s):  
Tim Vanuytsel ◽  
Sander van Wanrooy ◽  
Hanne Vanheel ◽  
Christophe Vanormelingen ◽  
Sofie Verschueren ◽  
...  
Keyword(s):  
Mast Cell ◽  
Psychological Stress ◽  
Intestinal Permeability ◽  
Corticotropin Releasing Hormone ◽  
Releasing Hormone ◽  
Dependent Mechanism
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