共查询到20条相似文献,搜索用时 31 毫秒
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In zebra finches, the vocal organ (syrinx) is larger in males than in females. Specific details about the mechanisms responsible for this dimorphism are not known, but may involve sex differences in steroid hormone action early in post-hatching development. The distribution of androgen receptor (AR), aromatase (AROM), estrogen receptor (ER), and estrogen receptor (ER) mRNAs was examined at post-hatching days 3, 10 and 17. A low level of AR was equivalently expressed in the syrinx muscles of both sexes at all three ages. We detected no specific expression of AROM or ER mRNAs. In contrast, ER mRNA was detected in chondrocytes of the forming bone. The density of this expression increased with age as the chondrocytes hypertrophied, but did not differ between the sexes. Taken together, these data suggest that estrogens may act on cartilage/bone, and androgens may act on muscle fibers in early post-hatching development to influence syrinx morphology. However, the lack of a sex difference in steroid receptor mRNA expression in the syrinx suggests that, similar to the forebrain regions that control song, the interaction of androgens and estrogens with their receptors is not sufficient to induce full sexual differentiation of this organ. 相似文献
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Boergesen M Pedersen TÅ Gross B van Heeringen SJ Hagenbeek D Bindesbøll C Caron S Lalloyer F Steffensen KR Nebb HI Gustafsson JÅ Stunnenberg HG Staels B Mandrup S 《Molecular and cellular biology》2012,32(4):852-867
The liver X receptors (LXRs) are nuclear receptors that form permissive heterodimers with retinoid X receptor (RXR) and are important regulators of lipid metabolism in the liver. We have recently shown that RXR agonist-induced hypertriglyceridemia and hepatic steatosis in mice are dependent on LXRs and correlate with an LXR-dependent hepatic induction of lipogenic genes. To further investigate the roles of RXR and LXR in the regulation of hepatic gene expression, we have mapped the ligand-regulated genome-wide binding of these factors in mouse liver. We find that the RXR agonist bexarotene primarily increases the genomic binding of RXR, whereas the LXR agonist T0901317 greatly increases both LXR and RXR binding. Functional annotation of putative direct LXR target genes revealed a significant association with classical LXR-regulated pathways as well as peroxisome proliferator-activated receptor (PPAR) signaling pathways, and subsequent chromatin immunoprecipitation-sequencing (ChIP-seq) mapping of PPARα binding demonstrated binding of PPARα to 71 to 88% of the identified LXR-RXR binding sites. The combination of sequence analysis of shared binding regions and sequential ChIP on selected sites indicate that LXR-RXR and PPARα-RXR bind to degenerate response elements in a mutually exclusive manner. Together, our findings suggest extensive and unexpected cross talk between hepatic LXR and PPARα at the level of binding to shared genomic sites. 相似文献
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《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1999,724(1):65-72
Nicotinic acetylcholine receptor (nAChR) α3-subunits, β4-subunits, α3/β4-subunit combination and α4/β2-subunit combination were immobilized on chromatographic stationary phases and the binding affinities of the different nAChR subtypes were chromatographically evaluated. The observed relative binding affinities of epibatidine were α4/β2>α3/β4 and epibatidine did not bind at α3-subunits and β4-subunits. No significant difference in binding affinities was observed on the α4/β2 nAChRs immobilized in immobilized artificial membrane (IAM) particles and those sterically immobilized on Superdex 200 beads. The effects of mobile phase pH and ionic strength on the binding affinities of the α3/β4 nAChRs support were also investigated. The results are consistent with the proposed ligand–nAChR binding model in which a cationic center exists at the binding site. 相似文献
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Clemens Röhrl Stefanie Fruhwürth Sabine Maria Schreier Alfred Lohninger Andrea Dolischka Manfred Hüttinger Nina Zemann Marcela Hermann Witta Strobl Herbert Stangl 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2010,1801(2):198-204
Recent evidence suggests that scavenger receptor, class B, type I (SR-BI) plays a physiological role in VLDL metabolism. SR-BI was reported to mediate β-VLDL uptake; however, cellular details of this process are not well characterized. In the present study we show that SR-BI delivers cholesterol derived from β-VLDL to LDL receptor negative SR-BI over-expressing Chinese Hamster Ovarian cells (ldlA7-SRBI). Cell association of β-VLDL was ∼ 3 times higher after SR-BI over-expression, which was competed by β-VLDL, but only to a lesser extent by HDL and LDL. Almost all of the associated β-VLDL was located intracellularly, and therefore could not be released by a 50-fold excess of unlabeled β-VLDL. β-VLDL was degraded at a rate of 6 ng β-VLDL/mg cell protein and hour. In contrast to ldlA7 cells, β-VLDL association was competed by LDL in cells with a functional LDL receptor like CHO and HepG2 cells, indicating a strong impact of the LDL receptor in β-VLDL uptake. β-VLDL degradation was similar to ldlA7-SRBI cells. When β-VLDL uptake was followed using fluorescence microscopy, β-VLDL showed a different uptake pattern in SR-BI over-expressing cells, ldlA7-SRBI, compared to LDL receptor containing cells, CHO and HepG2. 相似文献
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Laurent-Emmanuel Monfoulet Claire Philippe Sylvie Mercier Véronique Coxam Yohann Wittrant 《Experimental biology and medicine (Maywood, N.J.)》2015,240(7):854-866
Osteoarthritis (OA) is an age-related degenerative joint disease. To date, its management is focused on symptoms (pain and inflammation). Studies suggest that fatty acids can reduce the expression of inflammatory and catalytic mediators, and improve in vivo joint function. Free fatty acid receptors (FFARs) such as G-protein coupled receptor 40 (GPR40) are proposed as attractive therapeutic targets to counteract inflammation and cartilage degradation observed in OA. This study aims to elucidate the involvement of GPR40 in OA. In this study, we used an in vitro model of OA, and surgically induced OA by ligament transection and partial meniscectomy in wild-type and GPR40 deficient mice. OA phenotype was investigated in vivo by histology and genes expression. We demonstrate that IL-1β-treated GPR40−/− chondrocytes secret more inflammatory mediators (nitric oxide, interleukin-6, prostaglandin E2) and active catabolic enzymes (metalloproteinase-2, -9 [MMP-2, MMP-9]), and show decreased anabolism (glycoaminoglycan) compared to GPR40+/+ cells. In accordance with these results, we show that GPR40−/− mice exhibit an aggravated OA-induced phenotype characterized by higher tidemark exposure, frequency of osteophyte formation and subchondral bone sclerosis. Altogether our results demonstrate that GPR40 deficiency leads to an extended OA phenotype, providing evidence that increasing GPR40 activity, by natural or synthetic ligands, could be a new strategy in the management of OA. 相似文献
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Gottschalk S 《Cytotherapy》2012,14(6):645-646
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Nogo-A is a major myelin associated inhibitor that blocks regeneration of injured axons in the central nervous system (CNS).Nogo-66 (a 66-residue domain of Nogo-A) expressed on the surface of oligodendrocytes has been shown to directly interact with Nogo-66 receptor 1 (NgR1).A number of additional components of NgR1 receptor complex essential for its signaling have been uncovered.However,detailed composition of the complex and its signaling mechanisms remain to be fully elucidated.In this study,we show that Nogo receptor 3 (NgR3),a paralog of NgR1,is a binding protein for NgR1.The interaction is highly specific because other members of the reticulin family,to which Nogo-A belongs,do not bind to NgR3.Neither does NgR3 show any binding activity with Nogo receptor 2 (NgR2),another NgR1 paralog.Majority of NgR3 domains are required for its binding to NgR1.Moreover,a truncated NgR3 with the membrane anchoring domain deleted can function as a decoy receptor to reverse neurite outgrowth inhibition caused by Nogo-66 in culture.These in vitro results,together with previously reported overlapping expression profile between NgR1 and NgR3,suggest that NgR3 may be associated with NgR1 in vivo and that their binding interface may be targeted for treating neuronal injuries. 相似文献
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Binding sites specific for inositol 1,4,5-trisphosphate (InsP3) have been demonstrated in sarcoplasmic reticulum vesicles isolated from heart muscle. Scatchard analysis of a binding isotherm indicated a high as well as a low affinity binding site [1]. In this study a comparison was made between InsP3 binding to crude microsomal membranes prepared from rat heart atria and ventricles respectively. Results obtained showed a four-fold higher incidence of binding to atrial membranes. Furthermore, the receptor populations of the atria and ventricles behaved differently during conditions causing fluctuations in tissue InsP3 levels, viz. ischaemia, reperfusion and 1-adrenergic stimulation. Reperfusion, as well as phenylephrine stimulation, caused an increase in InsP3 levels associated with down-regulation of the ventricular InsP3 receptor population while binding to atrial binding sites was elevated. In the ventricular population this down-regulation was the result of a reduction in Bmax alone with no changes in the Kd values of the high- or the low-affinity binding sites. The reason(s) for the differential response of the atrial and ventricular InsP3 receptor populations to changes in InsP3 levels, remains to be established. 相似文献
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The mechanisms of regulation, activation and signal transduction of the angiotensin II (Ang II) type 1 (AT1) receptor have been studied extensively in the decade after its cloning. The AT1 receptor is a major component of the renin-angiotensin system (RAS). It mediates the classical biological actions of Ang II. Among the structures required for regulation and activation of the receptor, its carboxyl-terminal region plays crucial roles in receptor internalization, desensitization and phosphorylation. The mechanisms involved in heterotrimeric G-protein coupling to the receptor, activation of the downstream signaling pathway by G proteins and the Ang II signal transduction pathways leading to specific cellular responses are discussed. In addition, recent work on the identification and characterization of novel proteins associated with carboxyl-terminus of the AT1 receptor is presented. These novel proteins will advance our understanding of how the receptor is internalized and recycled as they provide molecular mechanisms for the activation and regulation of G-protein-coupled receptors. 相似文献
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《Bioorganic & medicinal chemistry letters》2019,29(22):126664
Peroxisome Proliferator-Activated Receptor γ (PPARγ) is a nuclear receptor important for glucose homeostasis and insulin sensitivity. The anti-diabetic drugs thiazolidinediones improve insulin sensitivity by blocking PPARγ phosphorylation at S273; however, their full agonism on PPARγ also causes significant unwanted side effects. The indole derivative UHC1 displays insulin-sensitizing effect by acting as a partial agonist through the inhibition of PPARγ S273 phosphorylation, but without full agonist-associated side effects; however, its potency leaves much to be desired. Herein we report the design and synthesis of potent indole analogs as partial PPARγ agonists via the structure-activity relationship studies. Our studies revealed that vanillylamine and piperonyl benzylamine at Site 1 are favored to bind PPARγ with either biphenyl or 3-trifluoromethyl benzyl group at Site 2. In particular, compound WO91A with vanillylamine at Site 1 displays highly potent PPARγ binding affinity (IC50 = 16.7 nM), over 30-fold more potent than the parental compound UHC1, yet with less side effect-associated transactivation activity. 相似文献
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Toomre D 《The Journal of cell biology》2005,171(3):415-417
Plasma membrane organization and the potential role, or not, of lipid raft microdomains in signal transduction is a controversial topic. Cross-correlation fluorescent correlation spectroscopy (CC-FCS) shows promise as a new approach to rapidly probe protein-protein interactions in living cells during signal transduction. CC-FCS data from studies of IgE receptor signaling challenge models of large stable lipid raft signaling domains and reveal a new complexity in the dynamic (re)organization of signaling complexes. 相似文献
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van der Poel CE Spaapen RM van de Winkel JG Leusen JH 《Journal of immunology (Baltimore, Md. : 1950)》2011,186(5):2699-2704
IgG FcRs are important mediators of immunity and play a key role during Ab-based immunotherapy. Within the leukocyte IgG receptor family, only FcγRI is capable of IgG binding with high affinity. FcγRI exists as a complex of a ligand binding α-chain and an FcR γ-chain. The receptors' α-chain can, furthermore, elicit several functions independent of the ITAM-bearing FcR γ-chain. Functional implications of high-affinity IgG binding and mechanisms underlying FcR γ-chain-independent signaling remain unclear to this day. In this paper, we provide an overview of past literature on FcγRI and address the implications of recently described interactions between cytosolic proteins and the FcγRI α-chain, as well as cytokine-enhanced FcγRI immune complex binding. Furthermore, an analysis of potential polymorphisms within the FCGR1A gene is provided. 相似文献