共查询到20条相似文献,搜索用时 31 毫秒
1.
M. C. Ochoa C. Razquin G. Zalba M. A. Martínez-González J. A. Martínez A. Marti 《Journal of physiology and biochemistry》2008,64(2):127-133
It has been shown that NADPH oxidase plays a role in oxidative stress which has been involved in the development of metabolic syndrome. The ?930A/G polymorphism of the CYBA gene (that codes p22phox, a major component of the NADPH oxidase) has been associated with human hypertension and with a reduction in NADPH oxidase activity. In this work, we have examined the influence of the ?930A/G polymorphism on obesity risk and insulin resistance in a case-control study of Spanish subjects (n=313). In the obese group (n=159), there was a statistically significant association between the GG genotype of the ?930A/G polymorphism of the CYBA gene and fasting insulin levels and HOMA index. This outcome agrees with previous findings concerning functional analyses of this polymorphism and reinforces the hypothesis that insulin resistance is associated with oxidative stress. In conclusion, a protective effect in carriers of the ?930A/G, polymorphism of the p22phox gene against insulin resistance in a population of Spanish obese adults has been found. 相似文献
2.
Peng-Fei Zheng Rui-Xing Yin Chun-Xiao Liu Guo-Xiong Deng Yao-Zong Guan Bi-Liu Wei 《Journal of cellular and molecular medicine》2020,24(10):5772-5785
This study aimed to assess the relationship of 3 spectrin repeat containing nuclear envelope protein 1 (SYNE1) and 4 KH domain containing RNA binding (QK1) single nucleotide polymorphisms (SNPs), their haplotypes, gene-gene (G × G), gene-environment (G × E) interactions and hypercholesterolaemia (HCH) and hypertriglyceridaemia (HTG) in the Chinese Maonan minority. The genetic make-up of the SYNE1-QK1 SNPs in 1932 unrelated subjects (normal, 641; HCH, 649; and HTG, 642) was obtained by next-generation sequencing technologies. The genotypic frequencies of following SNPs were suggestively distinctive between the control and HCH groups (rs2623963, rs7745725, rs9459317, rs16897566), or between the control and HTG groups (rs2623963, rs1358317, rs7745725, rs1923608, rs16897566 SNPs; P < .05, respectively). Multiple-locus linkage disequilibrium analysis indicated that the identified SNPs were not inherited independently. Several haplotypes and gene-gene interaction haplotypes among the detected SNPs may be related with an increased morbidity of HCH (C-G-A, C-G-G and C-G-G-T-C-A-T) and HTG (C-G-G, G-T-G-C, C-G-G-G-T-G-C and C-G-G-T-C-A-T), whereas others may be related with an decreased risk of HCH (G-A-A, G-C-A-T, C-A-A-T-C-A-T and G-A-A-G-C-A-T) and HTG (G-A-A, G-C-A-T, C-A-A-T-C-A-T and G-A-A-G-C-A-T). The association evaluation based on haplotypes and gene-gene interactions could improve the power of detecting the risk of dyslipidaemia than anyone of SNP alone. There was significant three-locus model involving SNP-SNP, haplotype-haplotype/environment and G × G interactions (P < .05-0.001) that were detected by GMDR in HCH and HTG groups. Different interactions between genetic and environmental factors would produce different redundancy or synergy effects on the morbidity of HCH and/or HTG. 相似文献
3.
Nobuchika Suzuki Kouhei Tsumoto Nicole Hajicek Kenji Daigo Reiko Tokita Shiro Minami Tatsuhiko Kodama Takao Hamakubo Tohru Kozasa 《The Journal of biological chemistry》2009,284(8):5000-5009
The transient protein-protein interactions induced by guanine
nucleotide-dependent conformational changes of G proteins play central roles
in G protein-coupled receptor-mediated signaling systems. Leukemia-associated
RhoGEF (LARG), a guanine nucleotide exchange factor for Rho, contains an RGS
homology (RH) domain and Dbl homology/pleckstrin homology (DH/PH) domains and
acts both as a GTPase-activating protein (GAP) and an effector for
Gα13. However, the molecular mechanism of LARG activation
upon Gα13 binding is not yet well understood. In this study,
we analyzed the Gα13-LARG interaction using cellular and
biochemical methods, including a surface plasmon resonance (SPR) analysis. The
results obtained using various LARG fragments demonstrated that active
Gα13 interacts with LARG through the RH domain, DH/PH
domains, and C-terminal region. However, an alanine substitution at the RH
domain contact position in Gα13 resulted in a large decrease
in affinity. Thermodynamic analysis revealed that binding of
Gα13 proceeds with a large negative heat capacity change
(ΔCp°), accompanied by a positive entropy change
(ΔS°). These results likely indicate that the binding of
Gα13 with the RH domain triggers conformational
rearrangements between Gα13 and LARG burying an exposed
hydrophobic surface to create a large complementary interface, which
facilitates complex formation through both GAP and effector interfaces, and
activates the RhoGEF. We propose that LARG activation is regulated by an
induced-fit mechanism through the GAP interface of Gα13.Heterotrimeric G
proteins3 serve as key
molecular switches to transduce a large array of extracellular signals into
cells by actively alternating their conformations between GDP-bound inactive
and GTP-bound active forms. In the current model, the ligand-activated G
protein-coupled receptors (GPCRs) catalyze the exchange of GDP for GTP on
Gα subunits (1). Upon
activation, three switch regions in the Gα subunit undergo significant
conformational changes, followed by dissociation of the GTP-bound Gα
subunit from the Gβγ subunits. Both Gα-GTP and free
Gβγ interact with diverse downstream effectors to transmit
intracellular signals. The Gα subunit hydrolyzes bound GTP to GDP by its
intrinsic GTPase activity. This deactivation process is further accelerated by
GTPase-activating proteins (GAPs) such as regulator of G protein signaling
(RGS) proteins (2,
3). Gα-GDP dissociates
from effectors and re-associates with Gβγ to terminate the
signal.Although this model explains the basic concept of G protein signaling, the
molecular dynamics of interactions among GPCR, G protein, RGS protein, and
effector during the signaling process is not well understood. It has been
suggested that the GPCR signals are integrated into the intracellular
signaling network at the level of G proteins
(4). Accumulating evidence
suggests that the Gα subunit acts as the core of the signaling complex
at the membrane, which is formed through the transient protein-protein
interactions of multiple signaling components
(5,
6). Thus, the quantitative
analysis of the dynamic molecular interactions in the GPCR signaling complex
will be crucial to understanding various cellular processes.Gα12 and Gα13 subunits have been
demonstrated to regulate the activity of Rho GTPase through RhoGEFs, which
contain an N-terminal RGS homology domain (RH-RhoGEFs)
(7–10).
RH-RhoGEFs, which consist of p115RhoGEF/Lsc, PDZ-Rho-GEF/GTRAP48, and LARG in
mammalian species, directly link the activation of GPCRs by extracellular
ligands to the regulation of Rho activity in cells
(10–14).
All three RH-RhoGEFs contain an N-terminal RH domain, which specifically
recognizes the active form of Gα12 or Gα13
and central DH/PH domains characteristic of GEFs for Rho GTPases. It has been
demonstrated in vitro that LARG and p115RhoGEF serve as specific GAPs
for Gα12/13 through their RH domains and also as their
effectors to regulate Rho GTPase activation
(11–13).
A structural study has demonstrated that the interface of the RH domain of
p115RhoGEFs and a Gα13/i1 chimera is different from that of
the RGS domain of RGS4 and Gαi1
(7). The N-terminal small
element in the RH domain, which is required for GAP activity toward
Gα13, contacts the switch regions and the helical domain of
the Gα13/i1 chimera. The core module of the p115RhoGEF RH
domain binds to the region of Gα13/i1, which is
conventionally used for effector binding. These results suggest roles for the
RH domain in the stimulation of GEF activity by Gα13 in
addition to GAP activity. On the other hand, several studies have also
indicated that regions outside of RH domain of RH-RhoGEFs, particularly the
DH/PH domains, interact directly with activated Gα13
(11,
14,
15). In addition, we have
demonstrated recently that p115RhoGEF interacts with distinct surfaces of
Gα13 for the GAP reaction or GEF activity regulation
(16). However, the molecular
mechanism of LARG activation upon Gα13 binding is not clearly
understood.In this study, we have developed a quantitative method for the kinetic and
thermodynamic analysis of Gα13-effector interaction using
surface plasmon resonance (SPR) with sensor chips on which
Gα13 was immobilized. We examined the kinetics and
thermodynamics of the Gα13-LARG interaction and assessed LARG
activation using both in vitro and cell-based approaches. We present
evidence that, in addition to the interaction with the RH domain, the DH/PH
domains and C-terminal region of LARG also interact with Gα13
to form the high affinity Gα13-LARG complex and activate
RhoGEF activity. We further propose that LARG adopts the active conformation
using an induced-fit mechanism through association with the GAP interface of
Gα13. A similar mechanism may also be used with other
Gα-effector interactions. 相似文献
4.
Sarecka-Hujar B Zak I Emich-Widera E Kopyta I Pilarska E Pienczk-Reclawowicz K 《Cell biochemistry and function》2010,28(7):591-596
Genes related to platelet and arterial endothelial function have been recently considered as independent risk factors for stroke. We aimed to analyze a relationship between the E‐selectin 98G > T polymorphism and stroke in children and to observe the transmission of E‐selectin alleles from heterozygous parents to their affected children. We studied 59 children after stroke, 112 parents, and 87 healthy children. The E‐selectin 98G > T polymorphism was analyzed with the polymerase chain reaction‐restriction fragment length polymorphism (PCR‐RFLP) method. The frequency of the 98T allele in patients was almost twofold lower than in controls (5.1% vs. 9.8%, p = 0.145, odds ratios (OR) = 0.49) as well as carriers of the 98T allele (19.5% in controls vs. 8.5% in cases, p = 0.067, OR = 0.38). The G allele of the E‐selectin 98G > T polymorphism was more frequently transmitted to the children after stroke compared to the T allele (68% vs. 32%). In conclusion, we did not confirm the relationship between the 98G > T polymorphism of the E‐selectin gene and childhood ischemic stroke. There is still a need for further studies. Copyright © 2010 John Wiley & Sons, Ltd. 相似文献
5.
Khandekar Jishan Bari Shrikant Sharma Kandala V. R. Chary 《Biomolecular NMR assignments》2018,12(1):51-55
γS-crystallin is a major structural component of the human eye lens, which maintains its stability over the lifetime of an organism with negligible turnover. The G57W mutant of human γS-crystallin (abbreviated hereafter as γS-G57W) is associated with dominant congenital cataracts. In order to provide a structural basis for the ability of γS-G57W causing cataract, we have cloned, overexpressed, isolated and purified the protein. The 2D [15N–1H]-HSQC spectrum recorded with uniformly 13C/15N-labelled γS-G57W was highly dispersed indicating the protein to adopt an ordered conformation. In this paper, we report almost complete sequence-specific 1H, 13C and 15N resonance assignments of γS-G57W using a suite of heteronuclear 3D NMR experiments. 相似文献
6.
Fibrinogen is a plasma protein that has been reported to be associated with an increased risk of atherothrombotic diseases and venous thrombosis. The most common polymorphism that has been studied so far in different populations is the G-455-->A polymorphism in the promoter region of the beta-fibrinogen gene. We studied 160 healthy unrelated Lebanese individuals for the prevalence of -455G/G, -455G/A and -455A/A genotypes of the beta-fibrinogen gene and the frequency of G and A alleles using a reverse hybridization PCR assay. The prevalence of the G/G, G/A, and A/A genotypes were found to be 60.6, 31.9 and 7.5%, respectively. The frequency of the G and A alleles were found to be 0.77 and 0.23, respectively. As compared to other ethnic groups, the Lebanese individuals were found to have a relatively high prevalence of the A allele which may predispose them to develop cardiovascular diseases as well as thrombotic events. This study provides additional unique genetic information pertaining to the Lebanese population. 相似文献
7.
RAPD and RFEL analyses revealed appreciable genetic heterogeneity of Rhizobium galegae bv. officinalis and R. galegae bv. orientalis, which are nitrogen-fixing symbiosis partners of Galega officinalis and G. orientalis, respectively, and do not form a single cross-inoculation group. Comparison of nucleotide and amino acid sequences for their lectins revealed relatively high general homology, testifying again to their close phylogenetic relationships. Yet the lectin region of the carbohydrate-binding peptide (CBP) proved to differ considerably, being TYCNPGWDPRDR in G. orientalis and TFYNEEWDLVIKDEH in G. officinalis. Conserved positions in the CBP were observed for amino acid residues involved in binding Ca2+ and Mn2+ and stabilizing the spatial structure of the carbohydrate-binding pocket. These findings confirm the role in Rhizobium— legume symbiosis for lectins and especially for their carbohydrate-binding domains.Translated from Molekulyarnaya Biologiya, Vol. 39, No. 1, 2005, pp. 103–111.Original Russian Text Copyright © 2005 by Baimiev, Gubaidullin, Chemeris, Vakhitov. 相似文献
8.
Ehlers C Weidenbach K Veit K Deppenmeier U Metcalf WW Schmitz RA 《Molecular genetics and genomics : MGG》2005,273(4):290-298
9.
Background
Luteinizing hormone-releasing hormone (LHRH) is an exogenous hormone commonly used to induce spermiation in anuran amphibians. Over the past few decades, the LHRH dose administered to individuals and the frequency of injection has been highly variable. The sperm-release responses reported have been correspondingly diverse, highlighting a need to quantify dose-response relationships on a species-specific basis. This study on the Australian anuran Pseudophryne guentheri first evaluated the spermiation response of males administered one of five LHRHa doses, and second, determined whether AVT administered in combination with the optimal LHRHa dose improved sperm-release. 相似文献10.
Background
Ovarian cancer G protein coupled receptor 1 (OGR1) mediates inhibitory effects on cell migration in human prostate and ovarian cancer cells. However, the mechanisms and signaling pathways that mediate these inhibitory effects are essentially unknown.Methods
MCF7 cell line was chosen as a model system to study the mechanisms by which OGR1 regulates cell migration, since it expresses very low levels of endogenous OGR1. Cell migratory activities were assessed using both wound healing and transwell migration assays. The signaling pathways involved were studied using pharmacological inhibitors and genetic forms of the relevant genes, as well as small G protein pull-down activity assays. The expression levels of various signaling molecules were analyzed by Western blot and quantitative PCR analysis.Results
Over-expression of OGR1 in MCF7 cells substantially enhanced activation of Rho and inhibition of Rac1, resulting in inhibition of cell migration. In addition, expression of the Gα12/13 specific regulator of G protein signaling (RGS) domain of p115RhoGEF, but not treatment with pertussis toxin (PTX, a Gαi specific inhibitor), could abrogate OGR1-dependent Rho activation, Rac1 inactivation, and inhibition of migration in MCF7 cells. The bioactive lipids tested had no effect on OGR1 function in cell migration.Conclusion
Our data suggest, for the first time, that OGR1 inhibits cell migration through a Gα12/13 -Rho-Rac1 signaling pathway in MCF7 cells. This pathway was not significantly affected by bioactive lipids and all the assays were conducted at constant pH, suggesting a constitutive activity of OGR1. This is the first clear delineation of an OGR1-mediated cell signaling pathway involved in migration.11.
《Bioorganic & medicinal chemistry》2014,22(13):3423-3434
Heterotrimeric G-proteins are the immediate downstream effectors of G-protein coupled receptors (GPCRs). Endogenous protein guanine nucleotide dissociation inhibitors (GDIs) like AGS3/4 and RGS12/14 function through GPR/Goloco GDI domains. Extensive characterization of GPR domain peptides indicate they function as selective GDIs for Gαi by competing for the GPCR and Gβγ and preventing GDP release. We modified a GPR consensus peptide by testing FGF and TAT leader sequences to make the peptide cell permeable. FGF modification inhibited GDI activity while TAT preserved GDI activity. TAT-GPR suppresses G-protein coupling to the receptor and completely blocked α2-adrenoceptor (α2AR) mediated decreases in cAMP in HEK293 cells at 100 nM. We then sought to discover selective small molecule inhibitors for Gαi. Molecular docking was used to identify potential molecules that bind to and stabilize the Gαi–GDP complex by directly interacting with both Gαi and GDP. Gαi–GTP and Gαq–GDP were used as a computational counter screen and Gαq–GDP was used as a biological counter screen. Thirty-seven molecules were tested using nucleotide exchange. STD NMR assays with compound 0990, a quinazoline derivative, showed direct interaction with Gαi. Several compounds showed Gαi specific inhibition and were able to block α2AR mediated regulation of cAMP. In addition to being a pharmacologic tool, GDI inhibition of Gα subunits has the advantage of circumventing the upstream component of GPCR-related signaling in cases of overstimulation by agonists, mutations, polymorphisms, and expression-related defects often seen in disease. 相似文献
12.
Takada M Nomura N Okada H Nakajima-Kambe T Nakahara T Uchiyama H 《Biotechnology letters》2005,27(12):871-874
Expression of the desulfurization genes (dsz) in Mycobacterium sp. G3 is repressed by sulfate, which is the product of biodesulfurization. An expression clone, pSMTABC, was constructed by placing the dsz genes downstream of the hsp60 promoter and the constructed plasmid was electroporated into G3. The recombinant strain G3-1 desulfurized dibenzothiophene in the presence of 0.5 mM sulfate while the Dsz phenotype was completely repressed in the wild-type strain. However, there was no significant increase in the amount of desulfurization enzymes in G3-1. In addition, G3 had superior separation of diesel oil–water separation activity compared to E. coli, which is superior to desulfurizing rhodococci. 相似文献
13.
Abstract
Cartilage tissues from the proboscis of skate (Raja porasa Günther) were used to initiate primary cultures of cartilage cells. Aseptically dissected cartilage tissues were immersed
in MEM medium free of fetal bovine serum (FBS), pH 7.6, and minced into small pieces (1 mm3 on average). After hydrolysis with collagenase II, hyaluronidase, and trypsin for 2 hours at room temperature, the acquired
cartilage cells were rinsed twice with 20% FBS-supplemented MEM medium and then inoculated into 25-cm3 cell culture flasks, and incubated at 24°C. The primary cultures were initiated successfully, and the cartilage cells grew
gradually into a confluent monolayer at day 10. Effects of growth factors were also tested in this study, and it was found
that 20 ng/ml of basic fibroblast growth factor and 100 ng/ml of insulin-like growth factor II together had the most prominent
stimulating effect on the growth and division of cartilage cells in the series of concentration combinations employed. The
induced cartilage cells cultured formed a confluent monolayer at day 7. 相似文献
14.
Methionine synthase (MTR) is required for the conversion of homocysteine (hcy) to methionine in the one-carbon metabolic pathway. Previous studies investigating a common MTR 2756A>G polymorphism as a maternal risk factor for the birth of a child with Down syndrome (DS) are conflicting and limited by small case–control cohorts, and its contribution to circulating hcy levels is still debated. We performed a large case–control study and a meta-analysis of the literature to further address the role of MTR 2756A>G as a maternal risk factor for the birth of a child with DS. 286 mothers of a DS child (MDS) and 305 control mothers of Italian origin were included in the case–control study. Genotyping was performed by means of PCR/RFLP technique. Data on circulating levels of hcy, folates, and vitamin B12 were available for 189 MDS and 194 control mothers. The meta analysis of previous and present data involved a total of 8 studies (1,171 MDS and 1,402 control mothers). Both the case–control study and the meta-analysis showed no association of MTR 2756A>G with the maternal risk of birth of a child with DS (OR = 1.15; 95 % CI 0.85–1.55, and OR = 1.08; 95 % CI 0.93–1.25, respectively), even after stratification of the overall data available for the meta-analysis into ethnic groups. No association of the studied polymorphism with circulating levels of hcy, folates, and vitamin B12 was observed. Present data do not support a role for MTR 2756A>G as independent maternal risk factor for a DS birth. 相似文献
15.
Inga Preuß Barbara Kurig Bernd Nürnberg Joachim H.C. Orth Klaus Aktories 《Cellular signalling》2009,21(4):551-558
The mitogenic Pasteurella multocida toxin (PMT) is a major virulence factor of P. multocida, which causes Pasteurellosis in man and animals. The toxin activates the small GTPase RhoA, the MAP kinase ERK and STAT proteins via the stimulation of members of two G protein families, Gq and G12/13. PMT action also results in an increase in inositol phosphates, which is due to the stimulation of PLCβ via Gαq. Recent studies indicate that PMT additionally activates Gαi to inhibit adenylyl cyclase. Here we show that PMT acts not only via Gα but also through Gβγ signaling. Activation of Gβγ by PMT causes stimulation of phosphoinositide 3-kinase (PI3K) γ and formation of phosphatidylinositol-3,4,5-trisphosphate (PIP3) as indicated by the recruitment of a PIP3-binding pleckstrin homology (PH) domain-containing protein to the plasma membrane. Moreover, it is demonstrated that Gβγ is necessary for PMT-induced signaling via Gα. Mutants of Gαq incapable of binding or releasing Gβγ are not activated by PMT. Similarly, sequestration of Gβγ inhibits PMT-induced Gα-signaling. 相似文献
16.
The effect of the SNP g.18475 A>G in the 3′UTR of NCF4 on mastitis susceptibility in dairy cattle
Zhihua Ju Changfa Wang Xiuge Wang Chunhong Yang Yan Zhang Yan Sun Qiang Jiang Rongling Li Jianbin Li Jifeng Zhong Jinming Huang 《Cell stress & chaperones》2018,23(3):385-391
Neutrophil cytosolic factor 4 (NCF4) is a member of the nicotinamide adenine dinucleotide phosphate oxidase subunit. This protein functions as an essential factor in the host defense against the progression of bacterial infection. To explore the variability of the NCF4 gene and the susceptibility of cows to mastitis, NCF4 functional single nucleotide polymorphism (SNP) of the 3′ untranslated region (3′UTR) and its targeted microRNA (miRNA) were identified. One SNP g.18475 A>G in the 3′UTR of NCF4 was found within the binding seed region of bta-miR-2426. We constructed two recombinant pMIR-REPORT? vectors with the A or G allele in the g.18475 locus and transiently co-transfected the vectors in human embryo kidney 293T (HEK 293T) cells, along with bta-miR-2426 mimics. A luciferase assay indicated that this SNP affects the binding of NCF4 and bta-miR-2426. In addition, the association analysis results showed that cows with the GG genotype in SNP g.18475 A>G had a relatively lower SCS value than cows with the AA genotype. Finally, quantitative real-time PCR (RT-qPCR) results showed that the cows with genotype GG had a relatively higher expression of NCF4 mRNA compared to the cows with genotype AA. NCF4 expression was regulated by the miRNA–mRNA interaction mechanism, and an important role for NCF4 in mastitis susceptibility in dairy cow was suggested. 相似文献
17.
Jianyun Huang Yutong Sun J. Jillian Zhang Xin-Yun Huang 《The Journal of biological chemistry》2015,290(1):272-283
G protein-coupled receptors (GPCRs) relay extracellular signals mainly to heterotrimeric G-proteins (Gαβγ) and they are the most successful drug targets. The mechanisms of G-protein activation by GPCRs are not well understood. Previous studies have revealed a signal relay route from a GPCR via the C-terminal α5-helix of Gα to the guanine nucleotide-binding pocket. Recent structural and biophysical studies uncover a role for the opening or rotating of the α-helical domain of Gα during the activation of Gα by a GPCR. Here we show that β-adrenergic receptors activate eight Gαs mutant proteins (from a screen of 66 Gαs mutants) that are unable to bind Gβγ subunits in cells. Five of these eight mutants are in the αF/Linker 2/β2 hinge region (extended Linker 2) that connects the Ras-like GTPase domain and the α-helical domain of Gαs. This extended Linker 2 is the target site of a natural product inhibitor of Gq. Our data show that the extended Linker 2 is critical for Gα activation by GPCRs. We propose that a GPCR via its intracellular loop 2 directly interacts with the β2/β3 loop of Gα to communicate to Linker 2, resulting in the opening and closing of the α-helical domain and the release of GDP during G-protein activation. 相似文献
18.
Karim Melliti Ulises Meza Rory Fisher Brett Adams 《The Journal of general physiology》1999,113(1):97-110
Regulators of G protein signaling (RGS) proteins bind to the α subunits of certain heterotrimeric G proteins and greatly enhance their rate of GTP hydrolysis, thereby determining the time course of interactions among Gα, Gβγ, and their effectors. Voltage-gated N-type Ca channels mediate neurosecretion, and these Ca channels are powerfully inhibited by G proteins. To determine whether RGS proteins could influence Ca channel function, we recorded the activity of N-type Ca channels coexpressed in human embryonic kidney (HEK293) cells with G protein–coupled muscarinic (m2) receptors and various RGS proteins. Coexpression of full-length RGS3T, RGS3, or RGS8 significantly attenuated the magnitude of receptor-mediated Ca channel inhibition. In control cells expressing α1B, α2, and β3 Ca channel subunits and m2 receptors, carbachol (1 μM) inhibited whole-cell currents by ∼80% compared with only ∼55% inhibition in cells also expressing exogenous RGS protein. A similar effect was produced by expression of the conserved core domain of RGS8. The attenuation of Ca current inhibition resulted primarily from a shift in the steady state dose–response relationship to higher agonist concentrations, with the EC50 for carbachol inhibition being ∼18 nM in control cells vs. ∼150 nM in RGS-expressing cells. The kinetics of Ca channel inhibition were also modified by RGS. Thus, in cells expressing RGS3T, the decay of prepulse facilitation was slower, and recovery of Ca channels from inhibition after agonist removal was faster than in control cells. The effects of RGS proteins on Ca channel modulation can be explained by their ability to act as GTPase-accelerating proteins for some Gα subunits. These results suggest that RGS proteins may play important roles in shaping the magnitude and kinetics of physiological events, such as neurosecretion, that involve G protein–modulated Ca channels. 相似文献
19.
W. W. W. DE JONG 《Nature: New biology》1971,234(49):176-177
STUDIES of adult1 and foetal2 haemoglobin from the chimpanzee (Pan troglodytes) have shown that the amino-acid compositions of tryptic and chymotryptic peptides of the α, β and γ-chains are indistinguishable from those of man. The primary structures of chimpanzee α, β and γ-chains are therefore almost certainly identical to the homologous human chains. The two types of γ-chains found in man3, Gγ and Aγ, with glycine and alanine in position γ136, respectively, are likewise present in the chimpanzee2. 相似文献
20.
AMIT KUMAR MADESHIYA SHRADDHA SINGH SHIPRA DWIVEDI RITURAJ KONWAR SHANKAR MADHAV NATU ASHIM GHATAK 《Journal of genetics》2017,96(1):53-64
Metabolic syndrome (MetS) is an inflammatory disorder, in which various cytokines play important role in tilting balance towards disease state. Interleukin-10 (IL-10) is an important antiinflammatory cytokine, but its genetic polymorphisms and serum levels in Indian MetS subjects are unknown. Three IL-10 gene polymorphisms (?1082A >G (rs1800896), ?819C >T (rs1800872) and ?592C >A (rs1800871)) were genotyped with PCR-RFLP in MetS subjects (n = 384) and age/sex matched control subjects (n = 386). Serum IL-10 was measured using enzyme-linked immunosorbent assay. Serum IL-10 level was significantly low in MetS subject and significantly correlated with clinicobiochemical parameters of MetS. Of three investigated promoter polymorphisms, IL-10 –819C > T and –592C >A were significantly associated with risk of MetS. The mutant alleles ?819T and ?592A of IL-10 gene polymorphism were significantly higher in MetS subjects compared to controls. Of the four different haplotypes obtained, common ACC haplotype and rare GTA haplotype of IL-10 polymorphisms were associated with MetS. The mean of fasting insulin and HOMA-IR were significantly different between the genotypes of both ?819 C >T and ?592C >A polymorphisms of IL-10 in MetS subjects. These results suggested that polymorphisms in IL-10 gene (?819C >T and ?592C >A), haplotypes (ACC and GTA) and serum level are significantly associated with risk of MetS. IL-10 ?819C >T and ?592C >A polymorphic variants are also significantly associated with insulin level and homeostasis model assessment-insulin resistance in north Indian MetS subjects. 相似文献