ABSTRACT
; β-adrenergic receptors (β-ARs) are widely found in organs of the human body and play an important role in regulating heart function, blood vessel dilation, energy metabolism, etc. Studies have shown that β-ARs are abnormally high in breast cancer cells, which can promote the occurrence and development of breast cancer by affecting the growth and metabolism of breast cancer, invasive metastasis, and angiogenesis. Clinical studies have shown that blocking β-ARs signaling improves the prognosis of breast cancer patients, so β-ARs may be a potential treatment target for breast cancer. This paper summarizes the role of β-ARs in the development of breast cancer, with a view to providing some reference for follow-up research and clinical treatment.
ABSTRACT
AIM:To investigate the regulation ofβ-adrenergic receptor (β-AR) agonist isoproterenol (ISO) on cardiac microRNA-21 (miR-21) expression.METHODS:The primary cultured mouse cardiomyocytes and cardiac fibroblasts were isolated by enzyme digestion and treated with ISO at 10μmol/L for 1, 6, 12, 24 and 48 h.The expression of miR-21 was detected by real-time PCR.The protein levels of p-STAT3 and STAT3 were determined by Western blot, and the concentration of interleukin-6 (IL-6) in the cultured supernatant was measured by ELISA.The cells were transfected with the luciferase reporter gene plasmid p GL3-21PPR containing the miR-21 promoter region, and the luciferase reporter gene assay was used to examine the effect of conditioned medium on the transcriptional activity of miR-21.RESULTS:The medium supernatant produced by ISO on cardiac fibroblasts was used as the conditioned medium, which increased the miR-21 expression in the cardiomyocytes in a time-dependent manner after fibroblasts was treated with ISO (P<0.05).The conditioned medium caused a significant increase in the transcriptional activity of miR-21 in the cardiomyocytes, while24 h and 48 h conditioned medium increased the transcriptional activity by 94.9％and 77.1％, respectively (P<0.01).The concentration of IL-6 in the conditioned medium was significantly increased, and the activity of transcriptional factor STAT3 was enhanced by paracrine action of IL-6 in the cardiomyocytes, which promoted the transcription and expression of miR-21.CONCLUSION:β-AR stimulation induces fibroblast synthesis and expression of IL-6 with paracrine effect on cardiomyocytes, up-regulates the expression of miR-21 in cardiomyocytes by IL-6/STAT3 pathway, and participates in the cardiac remodeling.
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Aim To explore the effects of depression on tumors, as well as its molecular mechanisms. Methods The chronic unpredictable mild stress model (CUMS) was constructed. Tumor was inoculated after behavioral test, and the differences in serum norepinephrine and tumor volume between groups were detected. Breast cancer cells were stimulated by administration and invasion, migration, proliferation and cell cycle distribution were detected. Western blot and immunofluorescence were utilized to detect cell surface receptors and intracellular signaling pathways. Results Depression up-regulated the level of norepinephrine (N E) and increased the phosphorylation of p38 MAPK, resulting in increased malignancy of breast cancer cells. Conclusions Depression may increase the malignancy of breast cancer through norepinephrine-induced p38 MAPK signaling pathway, thus increasing the malignant degree of breast cancer.
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Insulin resistance is characterized by the reduced ability of insulin to stimulate tissue uptake and disposal of glucose including cardiac muscle. These conditions accelerate the progression of heart failure and increase cardiovascular morbidity and mortality in patients with cardiovascular diseases. It is noteworthy that some conditions of insulin resistance are characterized by up-regulation of the sympathetic nervous system, resulting in enhanced stimulation of β-adrenergic receptor (βAR). Over-stimulation of βARs leads to the development of heart failure and is associated with the pathogenesis of insulin resistance in the heart. However, pathological consequences of the cross-talk between the βAR and the insulin sensitivity and the mechanism by which βAR over-stimulation promotes insulin resistance remain unclear. This review article examines the hypothesis that βARs over-stimulation leads to induction of insulin resistance in the heart.
Subject(s)
Humans , Cardiovascular Diseases , Cyclic AMP-Dependent Protein Kinases , Glucose , Heart Diseases , Heart Failure , Heart , Insulin Resistance , Insulin , Mortality , Myocardium , Sympathetic Nervous System , Up-RegulationABSTRACT
Interstitial cystitis (IC) is a debilitating disease characterized by chronic inflammation of the urinary bladder. β-Adrenergic receptor blockers appear to have a beneficial clinical effect in IC. In this paper, we review the evidence of an association between β-adrenergic receptor blockade and IC. The information was obtained from MEDLINE. Genetic studies have provided the opportunity to determine which proteins link β-adrenergic receptor blockade to IC pathology. In particular, this link involves the major histocompatibility complex class II molecules, the renin-angiotensin system, the transcription factor nuclear factor-κB, the nerve growth factor, and the vascular endothelial growth factor. Β-Adrenergic receptor blockers also exert anti-IC effects through non-genomic factors, including stress, mitogen-activated protein kinase pathways, prostaglandins, cyclooxygenase-2, oxidative stress, and nitric oxide synthase. In conclusion, β-adrenergic receptor blockade may play a beneficial role in IC treatment. Additional investigations that examine β-adrenergic receptor blockers as IC therapeutics are required to further elucidate this role.
ABSTRACT
The prevalent rates of overweight and obesity are steadily increasing all over the world. Previous studies of some candidate genes have indicated that most of the genes are associated with obesity in human adipose tissue. As much as 40% of the variations in body mass could be attributed to genetic difference. The β-adrenergic receptor (β-AR) plays a major role in the regulation of energy balance in humans. A high sympathetic nervous system activity has been shown to be associated with obesity and is believed to have pathogenetic relevance. Several common single nucleotide polymorphisms (SNPs) including Gly389Arg in β1-AR, Gln27Glu in β2-AR, and Trp64Arg in β3-AR in humans could alter receptor function and these variations ofβ-ARs were shown to have certain association with obesity. Here we summarize the genetic polymorphisms of human β-ARs and their potential impacts to obesity.
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Since many patients are still dying from asthma and COPD, developing more effective drugs with little side-effect which can be taken for a long time, is very important. Clinical usage of herbal medicines for chronic airway diseases has been increasing. Bakumondo-to is a useful herbal medicine with little side-effect for the treatment of chronic airway diseases. There are some similarities of pharmacological profile of herbal medicines to those of glucocorticoids. Although the regulation of gene expression by glucocorticoids has been clarified, that of Bakumondo-to is not well known. Elucidation of the mechanism of Bakumondo-to will be helpful in establishing a more effective treatment of chronic airway diseases. This article focuses on the regulation of gene expression by Bakumondo-to in airway epithelial cells, and describes the increase in mRNA expression for β-adrenergic receptors by Bakumondo-to and in glucocorticoid-sensitive promoter activity. We also discuss the mechanisms of the regulatory action of Bakumondo-to.
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The present study was designed to provide more extensive information on the effects of chronic <I>in vivo</I> β-adrenergic stimulation as produced in two different fashions, one through exercise training and the other through the chronic administration of isoproterenol, on the characteristics of β-adrenergic receptors (β-AR) in rat adipocyte membranes.<BR>1. The chronic administration of isoproterenol (2.5 mg/kg BW sc, daily for 21 days; IPR-treatment) significantly reduced lipolysis induced by noradrenaline in isolated adipocytes. However, exercise training (8 weeks of treadmill running) significantly increased the lipolytic response of adipocytes to noradrenaline.<BR>2. IPR-treatment significantly decreased the percentage of the high affinity state (%R<SUB>H</SUB>) and increased the dissociation constants of the high affinity state (K<SUB>H</SUB>) of β-AR in computer modeling of (-) -noradrenaline competition curves. However, exercise training significantly increased %R<SUB>H</SUB>.<BR>In conclusion, IPR-treatment reduced the lipolytic response of adipocytes to noradrenaline, at least partially, which resulted in the decreased formation of the high affinity state of β-AR. Exercise training may enhance the lipolytic ability of adipocytes to catecholamines through facilitating the formation of the high affinity state of β-AR.
ABSTRACT
The present study was designed to provide more extensive information on the effects of chronic <I>in vivo</I> β-adrenergic stimulation as produced in two different fashions, one through exercise training and the other through the chronic administration of isoproterenol, on the characteristics of β-adrenergic receptors (β-AR) in rat adipocyte membranes.<BR>1. The chronic administration of isoproterenol (2.5 mg/kg BW sc, daily for 21 days; IPR-treatment) significantly reduced lipolysis induced by noradrenaline in isolated adipocytes. However, exercise training (8 weeks of treadmill running) significantly increased the lipolytic response of adipocytes to noradrenaline.<BR>2. IPR-treatment significantly decreased the percentage of the high affinity state (%R<SUB>H</SUB>) and increased the dissociation constants of the high affinity state (K<SUB>H</SUB>) of β-AR in computer modeling of (-) -noradrenaline competition curves. However, exercise training significantly increased %R<SUB>H</SUB>.<BR>In conclusion, IPR-treatment reduced the lipolytic response of adipocytes to noradrenaline, at least partially, which resulted in the decreased formation of the high affinity state of β-AR. Exercise training may enhance the lipolytic ability of adipocytes to catecholamines through facilitating the formation of the high affinity state of β-AR.