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Gα 0

Filip Mundt, Magali Merrien, Lina Nygren, Lesley A Sutton, Birger Christensson, Björn E Wahlin, Richard Rosenquist, Birgitta Sander, Agata M Wasik
Mantle cell lymphoma (MCL), a malignancy of B-lymphocytes, has a poor prognosis. It is thus necessary to improve the understanding of the pathobiology of MCL and identify factors contributing to its aggressiveness. Our studies, based on Affymetrix data from 17 MCL biopsies, real-time quantitative polymerase chain reaction data from 18 sorted primary MCL cells and 108 MCL biopsies compared to non-malignant tissue, reveals that GNAZ expression predicts poor clinical outcome of MCL patients (Cox regression, P = 0·014) and lymphocytosis (Mann-Whitney, P = 0·011)...
February 20, 2019: British Journal of Haematology
Kazim Sahin, Fatih Akdemir, Cemal Orhan, Mehmet Tuzcu, Hasan Gencoglu, Nurhan Sahin, Ibrahim H Ozercan, Shakir Ali, Ismet Yilmaz, Vijaya Juturu
PURPOSE: Zeaxanthin protects the macula from ocular damage due to light or radiation by scavenging harmful reactive oxygen species. In the present study, zeaxanthin product (OmniXan®; OMX), derived from paprika pods (Capsicum annum; Family-Solanaceae), was tested for its efficacy in the rat retina against photooxidation. METHODS: Forty-two male 8-week-old Wistar rats exposed to 12L/12D, 16L/8D and 24L/0D hours of intense light conditions were orally administrated either 0 or 100 mg/kg BW of zeaxanthin concentration...
December 4, 2018: Cutaneous and Ocular Toxicology
Timo Littmann, Takeaki Ozawa, Carsten Hoffmann, Armin Buschauer, Günther Bernhardt
The earlier an activation of a G protein-dependent signalling cascade at a G protein-coupled receptor (GPCR) is probed, the less amplificatory effects contribute to the measured signal. This is especially useful in case of a precise quantification of agonist efficacies, and is of paramount importance, when determining agonist bias in relation to the β-arrestin pathway. As most canonical assays with medium to high throughput rely on the quantification of second messengers, and assays affording more proximal readouts are often limited in throughput, we developed a technique with a proximal readout and sufficiently high throughput that can be used in live cells...
November 21, 2018: Scientific Reports
Donghwa Kim, Soomin Cho, Maria A Castaño, Reynold A Panettieri, Jung A Woo, Stephen B Liggett
Bitter taste receptor (TAS2R) agonists dilate airways by receptor-dependent smooth muscle relaxation. Besides coupling to relaxation, we have found that human airway smooth muscle (HASM) cell TAS2Rs activate (phosphorylate) ERK1/2, but the cellular effects are not known. Here we show in HASM cells that TAS2R agonists initially stimulate pERK1/2, but by 24 hrs cause a marked (50-70%) downregulation of pERK1/2 without a change in total ERK1/2. It was hypothesized that TAS2R agonists suppress cell growth through this pERK1/2 downregulation...
October 26, 2018: American Journal of Respiratory Cell and Molecular Biology
Hang Cao, Syed M Qadri, Elisabeth Lang, Lisann Pelzl, Anja T Umbach, Veronika Leiss, Lutz Birnbaumer, Bernd Nürnberg, Burkert Pieske, Jakob Voelkl, Meinrad Gawaz, Rosi Bissinger, Florian Lang
Gαi2 , a heterotrimeric G-protein subunit, regulates various cell functions including ion channel activity, cell differentiation, proliferation and apoptosis. Platelet-expressed Gαi2 is decisive for the extent of tissue injury following ischemia/reperfusion. However, it is not known whether Gαi2 plays a role in the regulation of platelet apoptosis, which is characterized by caspase activation, cell shrinkage and cell membrane scrambling with phosphatidylserine (PS) translocation to the platelet surface. Stimulators of platelet apoptosis include thrombin and collagen-related peptide (CoRP), which are further known to enhance degranulation and activation of αII b β3-integrin and caspases...
September 2018: Physiological Reports
Susana Mato, Fuencisla Pilar-Cuéllar, Elsa M Valdizán, Javier González-Maeso, Rafael Rodríguez-Puertas, Javier Meana, Joan Sallés, Benedicto Crespo-Facorro, Ángel Pazos
Brain endocannabinoid system is proposed to play a role in the pathogenesis of affective disorders. In the present study, we analyzed the functionality of the cannabinoid receptor type 1 (CB1 receptor) at different transduction levels in prefrontal cortex (PFC) of depressed suicide victims. We examined stimulation of [35 S]GTPγS binding, activation of Gα protein subunits and inhibition of adenylyl cyclase by the cannabinoid agonist WIN55,212-2, as well as [3 H]CP55,940 binding, in PFC homogenates from suicide victims with major depression (MD) and matched control subjects...
November 2018: Biochemical Pharmacology
Labe A Black, Celestine J Thomas, Gwendolyn N Nix, Michelle C Terwilliger, Stephen R Sprang, J B Alexander Ross
Resistance to Inhibitors of Cholinesterase A (Ric-8A) is a 60-kDa cytosolic protein that has chaperone and guanine nucleotide exchange (GEF) activity toward heterotrimeric G protein α subunits of the i, q, and 12/13 classes, catalyzing the release of GDP from Gα and subsequent binding of GTP. In the absence of GTP or GTP analogs, and subsequent to GDP release, Gα forms a stable nucleotide-free complex with Ric-8A. In this study, time-resolved fluorescence anisotropy measurements were employed to detect local motions of Gαi1 labeled at selected sites with Alexa 488 (C5) fluorescent dye (Ax) in the GDP, GTPγS (collectively, GXP), and Ric-8A-bound states...
August 23, 2016: Biophysical Journal
Anne Trinh, Irene Chan, Maria Alexiadis, Medina Pell, Beena Kumar, Peter J Fuller
BACKGROUND: Cushing's syndrome is rare during pregnancy and more commonly due to adrenal pathology, in contrast to the non-pregnant population. Increased levels of cortisol-binding globulin and placental production of corticotropin-releasing hormone and adrenocorticotropic hormone complicate the diagnostic strategies usually employed. CASE: A 32-year-old G1P0 at 15/40 gestation presented with severe peripheral oedema and excessive weight gain. Examination revealed pitting oedema to the abdominal wall, wide violaceous striae, moon facies and acne...
March 2016: Obstetric Medicine
Ying Dunkel, Kexin Diao, Nicolas Aznar, Lee Swanson, Lawrence Liu, Wenhong Zhu, Xiao-Yi Mi, Pradipta Ghosh
Gα-interacting vesicle-associated protein (GIV, aka Girdin) is a guanine exchange factor (GEF) for the trimeric G protein Gαi and a bona fide metastasis-related gene that serves as a platform for amplification of tyrosine-based signals via G-protein intermediates. Here we present the first exploratory biomarker study conducted on a cohort of 187 patients with breast cancer to evaluate the prognostic role of total GIV (tGIV) and tyrosine phosphorylated GIV (pYGIV) across the various molecular subtypes. A Kaplan-Meier analysis of recurrence-free survival showed that the presence of tGIV, either cytoplasmic or nuclear, carried poor prognosis, but that nuclear tGIV had a greater prognostic impact (P = 0...
November 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Grit Schröter, Daniel Mann, Carsten Kötting, Klaus Gerwert
Gα subunits are central molecular switches in cells. They are activated by G protein-coupled receptors that exchange GDP for GTP, similar to small GTPase activation mechanisms. Gα subunits are turned off by GTP hydrolysis. For the first time we employed time-resolved FTIR difference spectroscopy to investigate the molecular reaction mechanisms of Gαi1. FTIR spectroscopy is a powerful tool that monitors reactions label free with high spatio-temporal resolution. In contrast to common multiple turnover assays, FTIR spectroscopy depicts the single turnover GTPase reaction without nucleotide exchange/Mg(2+) binding bias...
July 10, 2015: Journal of Biological Chemistry
JongYun Myeong, Misun Kwak, Jae-Pyo Jeon, Chansik Hong, Ju-Hong Jeon, Insuk So
TPRC channels are Ca(2+)-permeable, nonselective cation channels that are activated by a wide variety of stimuli, including G protein-coupled receptors (GPCRs). TRPC4 is commonly assumed to be activated by Gq/phospholipase C-coupled receptors. However, the other molecular mechanisms by which Gα proteins regulate TRPC4 remain unclear. Here, we found that Gαi2 regulates TRPC4 activation by direct binding. To investigate this mechanism, we used whole patch clamp and fluorescence resonance energy transfer (FRET)...
June 1, 2015: American Journal of Physiology. Cell Physiology
Rainer Girgert, Günter Emons, Carsten Gründker
BACKGROUND: Due to the lack of ERα, triple negative breast cancers (TNBCs) are not susceptible to endocrine therapy using antiestrogens. However, the majority of TNBCs express the membrane bound estrogen receptor GPR30. We have recently shown that knock-down of GPR30 expression prevented growth stimulation of TNBC cell lines by 17β-estradiol. Now we analyzed whether specific inhibition of GPR30 represents a new option for therapy of TNBC. METHODS: Growth of TNBC cells was assessed using Alamar-blue colorimetric assay...
2014: BMC Cancer
Li-Li Sang, Chun-Le Zhou, Lu Fu, Jing-Min Chong, Lin Zhang, Xian-Cun Cao, Hong Sun
The aim of the present study is to explore the mechanism of estrogen on regulating cardiac function disorder by adjusting the stimulating adenylate cyclase G α protein (Gαs)-cycle adenosine monophosphate (cAMP) signal pathway. Adult female rats were randomly divided into five groups: sham group, ovariectomized group (OVX), OVX and 17β-estradiol given group (OVX+E₂), OVX and isoprenaline injected group (OVX+ISO), OVX and 17β-estradiol, isoprenaline injected group (OVX+E₂+ISO). Rats were ovariectomized, and two weeks later, OVX+E₂group was injected with E₂, OVX+ISO group was injected with ISO, OVX+E₂+ISO group was injected with E₂and ISO...
October 25, 2014: Sheng Li Xue Bao: [Acta Physiologica Sinica]
Ting-ting Liu, Ti-long Ding, Yong Ma, Wei Wei
AIM: To explore the effects of noradrenaline (NA) on hepatic stellate cells (HSCs) in vitro and to determine the adrenoceptor (AR) subtypes and underlying mechanisms. METHODS: The distribution and expressions of α1A-, α1B-, and α1D-ARs in HSC-T6 cells were analyzed using immunocytochemistry and RT-PCR. Cell proliferation was evaluated with MTT assay. The expression of HSC activation factors [transforming factor-β1 (TGF-β1) and α-smooth muscle actin (α-SMA)], extracellular matrix (ECM) secretion factors [tissue inhibitor of metalloproteinase-1 (TIMP-1) and collagen-Ι (ColΙ)] and PKC-PI3K-AKT signaling components (PKC, PI3K, and AKT) in the cells were detected by Western blotting and RT-PCR...
November 2014: Acta Pharmacologica Sinica
Seonghee Lee, Clemencia M Rojas, Yasuhiro Ishiga, Sona Pandey, Kirankumar S Mysore
Heterotrimeric G-proteins have been proposed to be involved in many aspects of plant disease resistance but their precise role in mediating nonhost disease resistance is not well understood. We evaluated the roles of specific subunits of heterotrimeric G-proteins using knock-out mutants of Arabidopsis Gα, Gβ and Gγ subunits in response to host and nonhost Pseudomonas pathogens. Plants lacking functional Gα, Gβ and Gγ1Gγ2 proteins displayed enhanced bacterial growth and disease susceptibility in response to host and nonhost pathogens...
2013: PloS One
Stefanie Klenke, Winfried Siffert, Ulrich Hermann Frey
GNAQ and GNA11, encoding the G-proteins Gα(q) and Gα₁₁, are members of the Gα(q)/Gα₁₁ subfamily, which transmits signals from the cell surface to intracellular signalling cascades. The GNAQ promoter was already characterized, and regulation by the transcription factor early growth response 1 (Egr-1) was demonstrated. Interestingly, in silico analysis revealed putative Egr-1 binding sites in sequences potentially representing the GNA11 promoter. However, the GNA11 promoter has not been characterized so far...
November 2013: Basic & Clinical Pharmacology & Toxicology
C Aaron Monroy, Duncan I Mackie, David L Roman
G-protein coupled receptors are a diverse group that are the target of over 50% of marketed drugs. Activation of these receptors results in the exchange of bound GDP for GTP in the Gα subunit of the heterotrimeric G-protein. The Gα subunit dissociates from the β/γ subunits and both proceed to affect downstream signaling targets. The signal terminates by the hydrolysis of GTP to GDP and is temporally regulated by Regulators of G-protein Signaling (RGS) proteins that act as GTPase Activating Proteins (GAPs)...
2013: PloS One
M Estefanía López, Eldon R Rene, Luc Malhautier, Janick Rocher, Sandrine Bayle, María C Veiga, Christian Kennes
The biodegradation of gas-phase mixtures of methanol, α-pinene and H2S was examined in a biotrickling filter (BTF), inoculated with a microbial consortium composed of an autotrophic H2S-degrading culture, and pure strains of Candida boidinii, Rhodococcus erythropolis, and Ophiostoma stenoceras. The inlet concentrations of methanol, α-pinene and H2S varied from 0.05 to 3.3 gm(-3), 0.05 to 2.7 gm(-3), and 0.01 to 1.4 gm(-3), respectively, at empty bed residence times (EBRT) of either 38 or 26s. The maximum elimination capacities (ECmax) of the BTF were 302, 175, and 191 gm(-3)h(-1), with 100%, 67%, and >99% removal of methanol, α-pinene and H2S, respectively...
June 2013: Bioresource Technology
Jun-Min He, Xian-Ge Ma, Ying Zhang, Tie-Feng Sun, Fei-Fei Xu, Yi-Ping Chen, Xiao Liu, Ming Yue
Heterotrimeric G proteins have been shown to transmit ultraviolet B (UV-B) signals in mammalian cells, but whether they also transmit UV-B signals in plant cells is not clear. In this paper, we report that 0.5 W m(-2) UV-B induces stomatal closure in Arabidopsis (Arabidopsis thaliana) by eliciting a cascade of intracellular signaling events including Gα protein, hydrogen peroxide (H2O2), and nitric oxide (NO). UV-B triggered a significant increase in H2O2 or NO levels associated with stomatal closure in the wild type, but these effects were abolished in the single and double mutants of AtrbohD and AtrbohF or in the Nia1 mutants, respectively...
March 2013: Plant Physiology
Svetlana Tishchenko, Azat Gabdulkhakov, Uliana Tin, Olga Kostareva, Chen Lin, Vladimir L Katanaev
Regulator of G-protein signalling (RGS) proteins negatively regulate heterotrimeric G-protein signalling through their conserved RGS domains. RGS domains act as GTPase-activating proteins, accelerating the GTP hydrolysis rate of the activated form of Gα-subunits. Although omnipresent in eukaryotes, RGS proteins have not been adequately analysed in non-mammalian organisms. The Drosophila melanogaster Gαo-subunit and the RGS domain of its interacting partner CG5036 have been overproduced and purified; the crystallization of the complex of the two proteins using PEG 4000 as a crystallizing agent and preliminary X-ray crystallographic analysis are reported...
January 1, 2013: Acta Crystallographica. Section F, Structural Biology and Crystallization Communications
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