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排序方式: 共有283条查询结果,搜索用时 15 毫秒
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Yano N Ianus V Zhao TC Tseng A Padbury JF Tseng YT 《American journal of physiology. Heart and circulatory physiology》2007,293(1):H385-H393
Stimulation of cardiac beta-adrenergic receptors (beta-AR) activates both the G(s)- and G(i)-coupled signaling cascades, including the phosphoinositide 3 kinase (PI3K) pathway, that have important physiological implications. Multiple isoforms of PI3K exist in the heart. The goals of this study were to examine the intracellular signaling pathways linking beta-AR to PI3K and to identify the PI3K isoform mediating this transactivation in a cardiac context. Acute beta-AR stimulation with isoproterenol resulted in increased tyrosine kinase-associated PI3K activity and phosphorylation of Akt and p70S6K in H9c2 cardiomyocytes. Cotreatment with ICI-118,551, but not CGP-20712, abolished the increase in PI3K activity, suggesting a beta(2)-AR-mediated event. PI3K activation was also abrogated by cotreatment with pertussis toxin, 4-amino-5-(4-chlorophenyl)-7-(t-butyl)pyrazolol[3,4-d]pyrimidine (PP2, a selective Src-family tyrosine kinases inhibitor), or AG-1296 [selective platelet-derived growth factor receptor (PDGFR) inhibitor] but not with an inhibitor for protein kinase A, protein kinase C, Ras, adenylyl cyclase, epidermal growth factor receptor, or insulin-like growth factor-1 receptor. beta-AR stimulation induced an increase in tyrosine phosphorylation of PDGFR, which was abolished by inhibition of Src either by PP2 or small interfering RNA. Moreover, H9c2 cardiomyocytes stably transfected with a vector expressing a Gbetagamma sequestrant peptide derived from the COOH-terminus of beta-AR kinase-1 failed to activate PI3K after beta-AR stimulation, suggesting Gbetagamma is required for the transactivation. Furthermore, acute beta-AR stimulation in vivo resulted in increases in PDGFR-associated PI3K and PI3Kalpha isoform activities but not the activities of other isoforms (PI3Kbeta, -delta, -gamma) in adult mouse heart. Taken together, these data provide in vitro and in vivo evidence for a novel mechanism of beta-AR-mediated transactivation of cardiac PI3Kalpha via sequential involvement of Galpha(i)/Gbetagamma, Src, and PDGFR. 相似文献
94.
An NAD(P)H-Nicotine Blue Oxidoreductase Is Part of the Nicotine Regulon and May Protect Arthrobacter nicotinovorans from Oxidative Stress during Nicotine Catabolism
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95.
Luca Simon Vlad Miron Anca Ignatova Svetlana Skalicka-Woźniak Krystyna 《Phytochemistry Reviews》2019,18(2):377-403
Phytochemistry Reviews - Phenylethanoid glycosides (PhGs) and iridoids are two vast groups of water soluble secondary metabolites widely distributed in plant kingdom and well known for their... 相似文献
96.
Werner E. G. Müller Li Qiang Heinz C. Schröder Natalie Hönig Daoxian Yuan Vlad A. Grebenjuk Francesca Mussino Marco Giovine Xiaohong Wang 《Planta》2014,239(1):213-229
Karstification is a rapid process during which calcidic stones/limestones undergo dissolution with the consequence of a desertification of karst regions. A slow-down of those dissolution processes of Ca-carbonate can be approached by a reforestation program using karst-resistant plants that can resist alkaline pH and higher bicarbonate (HCO3 ?) concentrations in the soil. Carbonic anhydrases (CA) are enzymes that mediate a rapid and reversible interconversion of CO2 and HCO3 ?. In the present study, the steady-state expression of a CA gene, encoding for the plant carbonic anhydrase from the parsley Petroselinum crispum, is monitored. The studies were primarily been performed during germination of the seeds up to the 12/14-day-old embryos. The CA cDNA was cloned. Quantitative polymerase chain reaction (qPCR) analysis revealed that the gene expression level of the P. crispum CA is strongly and significantly affected at more alkaline pH in the growth medium (pH 8.3). This abolishing effect is counteracted both by addition of HCO3 ? and by addition of polyphosphate (polyP) to the culture medium. In response to polyP, the increased pH in the vacuoles of the growing plants is normalized. The effect of polyP let us to propose that this polymer acts as a buffer system that facilitates the adjustment of the pH in the cytoplasm. In addition, it is proposed that polyP has the potential to act, especially in the karst, as a fertilizer that allows the karstic plants to cope with the adverse pH and HCO3 ? condition in the soil. 相似文献
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98.
Ionita-Laza I Makarov V;ARRA Autism Sequencing Consortium Buxbaum JD 《American journal of human genetics》2012,90(6):1002-1013
Cluster-detection approaches, commonly used in epidemiology and astronomy, can be applied in the context of genetic sequence data for the identification of genetic regions significantly enriched with rare disease-risk variants (DRVs). Unlike existing association tests for sequence data, the goal of cluster-detection methods is to localize significant disease mutation clusters within a gene or region of interest. Here, we focus on a chromosome 2q replicated linkage region that is associated with autism spectrum disorder (ASD) and that has been sequenced in three independent datasets. We found that variants in one gene, LRP2, residing on 2q are associated with ASD in two datasets (the combined variable-threshold-test p value is 1.2 × 10(-5)). Using a cluster-detection method, we show that in the discovery and replication datasets, variants associated with ASD cluster preponderantly in 25 kb windows (adjusted p values are p(1) = 0.003 and p(2) = 0.002), and the two windows are highly overlapping. Furthermore, for the third dataset, a 25 kb region similar to those in the other two datasets shows significant evidence of enrichment of rare DRVs. The region implicated by all three studies is involved in ligand binding, suggesting that subtle alterations in either LRP2 expression or LRP2 primary sequence modulate the uptake of LRP2 ligands. BMP4 is a ligand of particular interest given its role in forebrain development, and modest changes in BMP4 binding, which binds to LRP2 near the mutation cluster, might subtly affect development and could lead to autism-associated phenotypes. 相似文献
99.
Costache V Bilotto S Laguerre L Bellé R Cosson B Cormier P Morales J 《Developmental biology》2012,365(1):303-309
The eukaryotic Initiation Factor 2 (eIF2) is a key regulator of protein synthesis in eukaryotic cells, implicated in the initiation step of translation. Fertilization of the sea urchin eggs triggers a rapid increase in protein synthesis activity, which is necessary for the progress into embryonic cell cycles. Here we demonstrate that fertilization triggers eIF2α dephosphorylation, concomitant with an increase in protein synthesis and that induction of the eIF2α phosphorylation is intimately linked with an inhibition of protein synthesis and cell cycle arrest. Using a phospho-mimetic protein microinjected into sea urchin eggs, we showed that dephosphorylation of eIF2α is necessary for protein synthesis activity and cell division progression following fertilization. Our results demonstrate that regulation of eIF2α plays an important role in the protein synthesis rise that occurs during early development following fertilization. 相似文献
100.
Ling A Plewe M Gonzalez J Madsen P Sams CK Lau J Gregor V Murphy D Teston K Kuki A Shi S Truesdale L Kiel D May J Lakis J Anderes K Iatsimirskaia E Sidelmann UG Knudsen LB Brand CL Polinsky A 《Bioorganic & medicinal chemistry letters》2002,12(4):663-666
A series of alkylidene hydrazide derivatives containing an alkoxyaryl moiety was optimized. The resulting hydrazide-ethers were competitive antagonists at the human glucagon receptor. Pharmacokinetic experiments showed fast clearance of most of the compounds tested. A representative compound [4-hydroxy-3-cyanobenzoic acid (4-isopropylbenzyloxy-3,5-dimethoxymethylene)hydrazide] with an IC50 value of 20 nM was shown to reduce blood glucose levels in fasted rats. 相似文献