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https://www.readbyqxmd.com/read/28202495/expression-of-grk2-and-igf1r-in-hepatocellular-carcinoma-clinicopathological-and-prognostic-significance
#1
Song-Bai Lin, Li Zhou, Zhi-Yong Liang, Wei-Xun Zhou, Ye Jin
AIM: It has been shown that G-protein-coupled receptor kinase 2 (GRK2) negatively regulates the insulin-like growth factor 1 receptor (IGF1R) signalling pathway in hepatocellular carcinoma (HCC). The aim of this study was to evaluate the clinicopathological and prognostic significance of GRK2 and IGF1R in HCC. METHODS: Expression of GRK2 and IGF1R was first detected by tissue microarray-based immunohistochemistry in 156 patients with HCC. Staining results, termed the H-score, were then correlated with clinicopathological variables and patient survival...
February 15, 2017: Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28193640/grk2-mediates-arginine-vasopressin-induced-il-6-production-via-nf-kb-signaling-in-neonatal-rat-cardiac-fibroblast
#2
Feifei Xu, Suzhen Sun, Xiaojun Wang, Eran Ni, Lingling Zhao, Weizhong Zhu
: Elevated interleukin 6(IL-6) levels in congestive heart failure are associated with myocardial damage during acute exacerbation and with chronic inflammation. Arginine vasopressin (AVP), a hormone released in response to cardiac stress, could be a factor of inflammation and fibrosis in the pathogenesis of heart failure. Recently, we have shown that AVP promotes the proliferation of neonatal rat cardiac fibroblasts (NRCFs) through a V1Avasopressin receptor-mediated G protein-coupled receptor kinase2 (GRK2) signaling...
February 13, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28187004/didymin-an-orally-active-citrus-flavonoid-for-targeting-neuroblastoma
#3
REVIEW
Sharad S Singhal, Sulabh Singhal, Preeti Singhal, Jyotsana Singhal, David Horne, Sanjay Awasthi
Neuroblastoma, a rapidly growing yet treatment responsive cancer, is the third most common cancer of children and the most common solid tumor in infants. Unfortunately, neuroblastoma that has lost p53 function often has a highly treatment-resistant phenotype leading to tragic outcomes. In the context of neuroblastoma, the functions of p53 and MYCN (which is amplified in ~25% of neuroblastomas) are integrally linked because they are mutually transcriptionally regulated, and because they together regulate the catalytic activity of RNA polymerases...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28162981/caveolin-1-and-g-protein-coupled-receptor-kinase-2-coregulate-endothelial-nitric-oxide-synthase-activity-in-sinusoidal-endothelial-cells
#4
Songling Liu, Richard T Premont, Shweta Singh, Don C Rockey
Liver injury leads to a vasculopathy in which post-translational modifications of endothelial nitric oxide synthase (eNOS) lead to impaired nitric oxide synthesis. We hypothesized that caveolin 1 (CAV1), a well-known eNOS interactor, regulates eNOS activity in sinusoidal endothelial cells (SECs) via its interaction with G-protein-coupled receptor kinase-2 (GRK2) that also post-translationally modifies eNOS. Liver injury with portal hypertension was established using bile duct ligation in rats. CAV1 function was modified using a CAV1 scaffolding domain construct and cDNAs encoding wild-type CAV1, and CAV1 phosphorylation was increased in injured SECs, resulting in increased GRK2-CAV1 interaction and decreased eNOS activity...
February 2, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28162602/-359-grk2-constitutively-downregulates-delta-opioid-receptor-activity-in-the-periphery
#5
A Doyle, R Gomez, M Henry, N Jeske
No abstract text is available yet for this article.
April 2016: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28148497/shear-stress-induces-g%C3%AE-q-11-activation-independent-of-g-protein-coupled-receptor-activation-in-endothelial-cells
#6
Nathaniel G Dela Paz, Benoît Melchior, John A Frangos
Mechanochemical signal transduction occurs when mechanical forces, such as fluid shear stress, are converted into biochemical responses within the cell. The molecular mechanisms by which endothelial cells (ECs) sense/transduce shear stress into biological signals, including the nature of the mechanosensor, are still unclear. G proteins and G protein-coupled receptors (GPCRs) have been postulated independently to mediate mechanotransduction. In this study, we used in situ proximity ligation assay (PLA) to investigate the role of a specific GPCR/Gαq/11 pair in EC shear stress-induced mechanotransduction...
February 1, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28137910/osteogenesis-is-improved-by-low-tumour-necrosis-factor-%C3%AE-concentration-through-the-modulation-of-gs-coupled-receptor-signals
#7
Simona Daniele, Letizia Natali, Chiara Giacomelli, Pietro Campiglia, Ettore Novellino, Claudia Martini, Maria Letizia Trincavelli
In the early phase of bone damage, low concentrations of the cytokine Tumour Necrosis factor-alpha (TNF-α) favour osteoblast differentiation. In contrast, chronic high doses of the same cytokine contribute to bone loss, demonstrating opposite effects in dependence on its concentration and on the time of exposure.In the bone microenvironment, TNF-α modulates the expression/function of different G protein coupled receptors (GPCRs) and of their regulatory proteins, GPCR regulated kinases (GRKs), thus dictating their final biological outcome in controlling bone anabolic processes...
January 30, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28130200/targeting-gpcr-g%C3%AE-%C3%AE-grk2-signaling-as-a-novel-strategy-for-treating-cardiorenal-pathologies
#8
REVIEW
Valeria Rudomanova, Burns C Blaxall
The pathologic crosstalk between the heart and kidney is known as cardiorenal syndrome (CRS). While the specific mechanisms underlying this crosstalk remain poorly understood, CRS is associated with exacerbated dysfunction of either or both organs and reduced survival. Maladaptive fibrotic remodeling is a key component of both heart and kidney failure pathogenesis and progression. G-protein coupled receptor (GPCR) signaling is a crucial regulator of cardiovascular and renal function. Chronic/pathologic GPCR signaling elicits the interaction of the G-protein Gβγ subunit with GPCR kinase 2 (GRK2), targeting the receptor for internalization, scaffolding to pathologic signals, and receptor degradation...
January 25, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28128420/grk2-desensitizes-flow-induced-responses-in-osteoblasts
#9
Y Xing, Y Gu, X Shan, L Wang, J You
Bone desensitization after mechanical loading is essential for bone to adapt to its mechanical environment. However, the desensitization mechanism is unknown. Previous studies suggest that G protein-coupled receptors (GPCRs), including P2Y and parathyroid hormone receptors, play important roles in osteoblast mechanobiology. Thus, for the present research, we examined the role of G protein-coupled receptor kinase 2 (GRK2) in osteoblast desensitization after exposure to mechanical stimulation. We first showed the existence of osteoblast desensitization after mechanical stimulation based on cytosol Ca(2+) and phosphorylated ERK1/2 activities, detected using a fluorescent Ca(2+)-sensitive dye and western blotting, respectively...
January 23, 2017: Genetics and Molecular Research: GMR
https://www.readbyqxmd.com/read/28112221/mincle-activation-enhances-neutrophil-migration-and-resistance-to-polymicrobial-septic-peritonitis
#10
Wook-Bin Lee, Ji-Jing Yan, Ji-Seon Kang, Quanri Zhang, Won Young Choi, Lark Kyun Kim, Young-Joon Kim
Sepsis is a systemic inflammatory response to bacterial infection. The therapeutic options for treating sepsis are limited. Impaired neutrophil recruitment into the infection site is directly associated with severe sepsis, but the precise mechanism is unclear. Here, we show that Mincle plays a key role in neutrophil migration and resistance during polymicrobial sepsis. Mincle-deficient mice exhibited lower survival rates in experimental sepsis from cecal ligation and puncture and Escherichia coli-induced peritonitis...
January 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077324/grk2-as-negative-modulator-of-no-bioavailability-implications-for-cardiovascular-disease
#11
REVIEW
Alessandro Cannavo, Walter J Koch
Nitric oxide (NO), initially identified as endothelium-derived relaxing factor (EDRF), is a gaso-transmitter with important regulatory roles in the cardiovascular, nervous and immune systems. In the former, this diatomic molecule and free radical gas controls vascular tone and cardiac mechanics, among others. In the cardiovascular system, it is now understood that β-adrenergic receptor (βAR) activation is a key modulator of NO generation. Therefore, it is not surprising that the up-regulation of G protein-coupled receptor kinases (GRKs), in particular GRK2, that restrains βAR activity contributes to impaired cardiovascular functions via alteration of NO bioavailability...
January 7, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28035008/regulator-of-g-protein-signaling-6-protects-the-heart-from-ischemic-injury
#12
Boyd R Rorabaugh, Bandana Chakravarti, Nathaniel W Mabe, Sarah L Seeley, Albert D Bui, Jianqi Yang, Stephanie W Watts, Richard R Neubig, Rory A Fisher
Gαi-coupled receptors play important roles in protecting the heart from ischemic injury. Regulator of G protein signaling (RGS) proteins suppress Gαi signaling by accelerating the GTPase activity of Gαi subunits. However, the roles of individual RGS proteins in modulating ischemic injury are unknown. In the present study, we investigated the impact of RGS6 deletion on myocardial sensitivity to ischemic injury. Hearts from RGS6 knockout (RGS6-/-) and wildtype (RGS6+/+) mice were subjected to 30 min ischemia and 2 hr reperfusion on a Langendorff heart apparatus...
December 29, 2016: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/27999776/-freeze-don-t-move-how-to-arrest-a-suspect-in-heart-failure-a-review-on-available-grk2-inhibitors
#13
REVIEW
Daniela Sorriento, Michele Ciccarelli, Ersilia Cipolletta, Bruno Trimarco, Guido Iaccarino
Cardiovascular disease and heart failure (HF) still collect the largest toll of death in western societies and all over the world. A growing number of molecular mechanisms represent possible targets for new therapeutic strategies, which can counteract the metabolic and structural changes observed in the failing heart. G protein-coupled receptor kinase 2 (GRK2) is one of such targets for which experimental and clinical evidence are established. Indeed, several strategies have been carried out in place to interface with the known GRK2 mechanisms of action in the failing heart...
2016: Frontiers in Cardiovascular Medicine
https://www.readbyqxmd.com/read/27992454/the-effects-of-swiprosin-1-on-the-formation-of-pseudopodia-like-structures-and-%C3%AE-adrenoceptor-coupling-in-cultured-adult-rat-ventricular-cardiomyocytes
#14
Franziska Nippert, Rolf Schreckenberg, Antonia Hess, Martin Weber, Klaus-Dieter Schlüter
BACKGROUND: Recent findings suggest that adult terminally differentiated cardiomyocytes adapt to stress by cellular de- and redifferentiation. In the present study we tested the hypothesis that swiprosin-1 is a key player in this process. Furthermore, the relationship between swiprosin-1 and β-adrenoceptor coupling was analyzed. METHODS: In order to study the function of swiprosin-1 in adult rat ventricular cardiomyocytes (ARVC) they were isolated and cultured in a medium containing 20% fetal calf serum (FCS)...
2016: PloS One
https://www.readbyqxmd.com/read/27895163/g-protein-coupled-receptor-kinase-2-grk2-as-a-potential-modulator-of-the-hallmarks-of-cancer
#15
Laura Nogues, Clara Reglero, Veronica Rivas, Maria Neves, Petronila Penela, Federico Mayor
Malignant features such as sustained proliferation, refractoriness to growth suppressors, resistance to cell death or aberrant motility and metastasis can be triggered by a variety of mutations and signaling adaptations. Signaling nodes can act as cancer-associated factors by cooperating with oncogene-governed pathways or participating in compensatory transduction networks to strengthen tumor properties. G-protein-coupled receptor kinase 2 (GRK2) is arising as one of such nodes. Via its complex network of connections with other cellular proteins, GRK2 contributes to the modulation of basic cellular functions such as cell proliferation, survival or motility, and is involved in metabolic homeostasis, inflammation or angiogenic processes...
November 28, 2016: Molecular Pharmacology
https://www.readbyqxmd.com/read/27865836/g-protein-coupled-receptor-kinase-2-upregulation-causes-%C3%AE%C2%BA-opioid-receptor-desensitization-in-diabetic-heart
#16
Xiyao Chen, Shihao Zhao, Yunlong Xia, Zhenyu Xiong, Yueyang Li, Ling Tao, Fuyang Zhang, Xiaoming Wang
Activation of κ-opioid receptor (KOR) ameliorates myocardial ischemia/reperfusion (I/R) injury; however, cardioprotective effects of KOR stimulation disappear in type 1 diabetic subjects with hyperglycemia. The molecular mechanisms underlying this phenomenon remain unknown. Here we found that KOR expression was obviously downregulated and KOR agonism-induced contractile-regulatory and cardioprotective effects were significantly impaired in hearts isolated from streptozotocin (STZ) injection-induced diabetic mice...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27862165/grk2-%C3%AE-arrestin-mediates-arginine-vasopressin-induced-cardiac-fibroblast-proliferation
#17
Yunxuan Chen, Feifei Xu, Lingling Zhang, Xiaojun Wang, Yifan Wang, AnthonyYiu-Ho Woo, Weizhong Zhu
Cardiac fibrosis is a pathological feature commonly foundinheartsexposed to hemodynamic orneurohormonal stress. Elevated levels of arginine vasopressin (AVP) are closely associated with the progression ofheart failure and could be an underlyingcauseof cardiac fibrosis. The aim of this study is to characterize the effect of AVP on neonatal rat cardiac fibroblasts (NRCFs) and to illustrate itssignallingmechanism. The proliferative effect of AVP was assessed by methylthiazolyldiphenyl-tetrazoliumassay and 5-bromo-2'-deoxyuridine (BrdU) incorporation assay, and the amounts of cellular signallingproteins α-smooth muscle actin(α-SMA),matrix metalloproteinase (MMP) 2, MMP9, and phosphorylated ERK1/2 were determined by Western blotting...
November 14, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27832814/obesity-induced-cardiac-lipid-accumulation-in-adult-mice-is-modulated-by-g-protein-coupled-receptor-kinase-2-levels
#18
Elisa Lucas, Rocio Vila-Bedmar, Alba C Arcones, Marta Cruces-Sande, Victoria Cachofeiro, Federico Mayor, Cristina Murga
BACKGROUND: The leading cause of death among the obese population is heart failure and stroke prompted by structural and functional changes in the heart. The molecular mechanisms that underlie obesity-related cardiac remodeling are complex, and include hemodynamic and metabolic alterations that ultimately affect the functionality of the myocardium. G protein-coupled receptor kinase 2 (GRK2) is an ubiquitous kinase able to desensitize the active form of several G protein-coupled receptors (GPCR) and is known to play an important role in cardiac GPCR modulation...
10, 2016: Cardiovascular Diabetology
https://www.readbyqxmd.com/read/27815373/inhibiting-insulin-mediated-%C3%AE-2-adrenergic-receptor-activation-prevents-diabetes-associated-cardiac-dysfunction
#19
Qingtong Wang, Yongming Liu, Qin Fu, Bing Xu, Yuan Zhang, Sungjin Kim, Ruensern Tan, Federica Barbagallo, Toni West, Ethan Anderson, Wei Wei, E Dale Abel, Yang K Xiang
BACKGROUND: Type 2 diabetes mellitus (DM) and obesity independently increase the risk of heart failure by incompletely understood mechanisms. We propose that hyperinsulinemia might promote adverse consequences in the hearts of subjects with type-2 DM and obesity. METHODS: High-fat diet feeding was used to induce obesity and DM in wild-type mice or mice lacking β2-adrenergic receptor (β2AR) or β-arrestin2. Wild-type mice fed with high-fat diet were treated with a β-blocker carvedilol or a GRK2 (G-protein-coupled receptor kinase 2) inhibitor...
January 3, 2017: Circulation
https://www.readbyqxmd.com/read/27773680/vasopressin-v1a-receptor-mediates-cell-proliferation-through-grk2-egfr-erk1-2-pathway-in-a7r5-cells
#20
Lingling Zhang, Xiaojun Wang, Hong Cao, Yunxuan Chen, Xianfan Chen, Xi Zhao, Feifei Xu, Yifan Wang, Anthony Yiu-Ho Woo, Weizhong Zhu
Abnormal proliferation and hypertrophy of vascular smooth muscle (VSMC), as the main structural component of the vasculature, is an important pathological mechanism of hypertension. Recently, increased levels of arginine vasopressin (AVP) and copeptin, the C-terminal fragment of provasopressin, have been shown to correlate with the development of preeclampsia. AVP targets on the Gq-coupled vasopressin V1A receptor and the Gs-coupled V2 receptor in VSMC and the kidneys to regulate vascular tone and water homeostasis...
December 5, 2016: European Journal of Pharmacology
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