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991.
Plasma membrane (PM) Na+, K+-ATPase, plays crucial roles in numerous physiological processes. Cardiac steroids (CS), such as ouabain and bufalin, specifically bind to the Na+, K+-ATPase and affect ionic homeostasis, signal transduction, and endocytosed membrane traffic. CS-like compounds, synthesized in and released from the adrenal gland, are considered a new family of steroid hormones. Previous studies showed that ouabain induces slow Ca2+ oscillations in COS-7 cells by enhancing the interactions between Na+, K+-ATPase, inositol 1,4,5-trisphosphate receptor (IP3R) and Ankyrin B (Ank-B) to form a Ca2+ signaling micro-domain. The activation of this micro-domain, however, is independent of InsP3 generation. Thus, the mechanism underlying the induction of these slow Ca2+ oscillations remained largely unclear. We now show that other CS, such as bufalin, can also induce Ca2+ oscillations. These oscillations depend on extracellular Ca2+ concentrations [Ca2+]out and are inhibited by Ni2+. Furthermore, we found that these slow oscillations are Na+out dependent, abolished by Na+/Ca2+ exchanger1 (NCX1)-specific inhibitors and markedly attenuated by NCX1 siRNA knockdown. Based on these results, a model is presented for the CS-induced slow Ca2+ oscillations in COS-7 cells. 相似文献
992.
Kawai M Breggia AC DeMambro VE Shen X Canalis E Bouxsein ML Beamer WG Clemmons DR Rosen CJ 《The Journal of biological chemistry》2011,286(16):14670-14680
Insulin-like growth factor-binding protein 2 (IGFBP-2) is a member of a family of six highly conserved IGFBPs that are carriers for the insulin-like growth factors (IGFs). IGFBP-2 levels rise during rapid neonatal growth and at the time of peak bone acquisition. In contrast, Igfbp2(-/-) mice have low bone mass accompanied by reduced osteoblast numbers, low bone formation rates, and increased PTEN expression. In the current study, we postulated that IGFBP-2 increased bone mass partly through the activity of its heparin-binding domain (HBD). We synthesized a HBD peptide specific for IGFBP-2 and demonstrated in vitro that it rescued the mineralization phenotype of Igfbp2(-/-) bone marrow stromal cells and calvarial osteoblasts. Consistent with its cellular actions, the HBD peptide ex vivo stimulated metacarpal periosteal expansion. Furthermore, administration of HBD peptide to Igfbp2(-/-) mice increased osteoblast number, suppressed marrow adipogenesis, restored trabecular bone mass, and reduced bone resorption. Skeletal rescue in the Igfbp2(-/-) mice was characterized by reduced PTEN expression followed by enhanced Akt phosphorylation in response to IGF-I and increased β-catenin signaling through two mechanisms: 1) stimulation of its cytosolic accumulation and 2) increased phosphorylation of serine 552. We conclude that the HBD peptide of IGFBP-2 has anabolic activity by activating IGF-I/Akt and β-catenin signaling pathways. These data support a growing body of evidence that IGFBP-2 is not just a transport protein but rather that it functions coordinately with IGF-I to stimulate growth and skeletal acquisition. 相似文献
993.
994.
Sofieke E Klamer Carlijn GM Kuijk Peter L Hordijk C Ellen van der Schoot Marieke von Lindern Paula B van Hennik Carlijn Voermans 《Cell Adhesion & Migration》2013,7(5):434-449
Cell adhesion and migration are important determinants of homing and development of hematopoietic stem and progenitor cells (HSPCs) in bone marrow (BM) niches. The extracellular matrix protein transforming growth factor-β (TGF-β) inducible gene H3 (BIGH3) is involved in adhesion and migration, although the effect of BIGH3 is highly cell type-dependent. BIGH3 is abundantly expressed by mesenchymal stromal cells, while its expression in HSPCs is relatively low unless induced by certain BM stressors. Here, we set out to determine how BIGH3 modulates HSPC adhesion and migration. We show that primary HSPCs adhere to BIGH3-coated substrates, which is, in part, integrin-dependent. Overexpression of BIGH3 in HSPCs and HL60 cells reduced the adhesion to the substrate fibronectin in adhesion assays, which was even more profound in electrical cell-substrate impedance sensing (ECIS) assays. Accordingly, the CXCL12 induced migration over fibronectin-coated surface was reduced in BIGH3-expressing HSPCs. The integrin expression profile of HSPCs was not altered upon BIGH3 expression. Although expression of BIGH3 did not alter actin polymerization in response to CXCL12, it inhibited the PMA-induced activation of the small GTPase RAC1 as well as the phosphorylation and activation of extracellular-regulated kinases (ERKs). Reduced activation of ERK and RAC1 may be responsible for the inhibition of cell adhesion and migration by BIGH3 in HSPCs. Induced BIGH3 expression upon BM stress may contribute to the regulation of BM homeostasis. 相似文献
995.
Lori A. Coburn Sara N. Horst Rupesh Chaturvedi Caroline T. Brown Margaret M. Allaman Brooks P. Scull Kshipra Singh M. Blanca Piazuelo Maithili V. Chitnavis Mallary E. Hodges Michael J. Rosen Christopher S. Williams James C. Slaughter Dawn B. Beaulieu David A. Schwartz Keith T. Wilson 《PloS one》2013,8(12)
Accurate and high-throughput technologies are needed for identification of new therapeutic targets and for optimizing therapy in inflammatory bowel disease. Our aim was to assess multi-analyte protein-based assays of cytokines/chemokines using Luminex technology. We have reported that Luminex-based profiling was useful in assessing response to L-arginine therapy in the mouse model of dextran sulfate sodium colitis. Therefore, we studied prospectively collected samples from ulcerative colitis (UC) patients and control subjects. Serum, colon biopsies, and clinical information were obtained from subjects undergoing colonoscopy for evaluation of UC or for non-UC indications. In total, 38 normal controls and 137 UC cases completed the study. Histologic disease severity and the Mayo Disease Activity Index (DAI) were assessed. Serum and colonic tissue cytokine/chemokine profiles were measured by Luminex-based multiplex testing of 42 analytes. Only eotaxin-1 and G-CSF were increased in serum of patients with histologically active UC vs. controls. While 13 cytokines/chemokines were increased in active UC vs. controls in tissues, only eotaxin-1 was increased in all levels of active disease in both serum and tissue. In tissues, eotaxin-1 correlated with the DAI and with eosinophil counts. Increased eotaxin-1 levels were confirmed by real-time PCR. Tissue eotaxin-1 levels were also increased in experimental murine colitis induced by dextran sulfate sodium, oxazolone, or Citrobacter rodentium, but not in murine Helicobacter pylori infection. Our data implicate eotaxin-1 as an etiologic factor and therapeutic target in UC, and indicate that Luminex-based assays may be useful to assess IBD pathogenesis and to select patients for anti-cytokine/chemokine therapies. 相似文献
996.
Geraldine Werhahn Yanjiang Liu Yao Meng Chen Cheng Zhi Lu Luciano Atzeni Zhixiong Deng Shi Kun Xinning Shao Qi Lu Jyoti Joshi Adarsh Man Sherchan Dibesh Karmacharya Hemanta Kumari Chaudhary Naresh Kusi Byron Weckworth Shannon Kachel Tatjana Rosen Zairbek Kubanychbekov Khalil Karimov Jennifer Kaden Muhammad Ghazali David W. Macdonald Claudio Sillero-Zubiri Helen Senn 《Journal of Biogeography》2020,47(6):1272-1285
997.
Jian Chen Jun Zhang Yi-Fei Wu Fang-Jie Zhao Barry P. Rosen 《Environmental microbiology》2021,23(12):7550-7562
Toxic organoarsenicals enter the environment from biogenic and anthropogenic activities such as microbial methylation of inorganic arsenic and pentavalent herbicides such as monosodium methylarsenate (MSMA or MAs(V)). Trivalent MAs(III) is considerably more toxic than arsenite or arsenate. Microbes have evolved mechanisms to detoxify organoarsenicals. We previously identified ArsV, a flavin-linked monooxygenase and demonstrated that it confers resistance to methylarsenite by oxidation to methylarsenate. The arsV gene is usually in an arsenic resistance (ars) operon controlled by an ArsR repressor and adjacent to a methylarsenite efflux gene, either arsK or a gene for a putative transporter. Here we show that Paracoccus sp. SY oxidizes methylarsenite. It has an ars operon with three genes, arsR, arsV and a transport gene termed arsW. Heterologous expression of arsV in Escherichia coli conferred resistance to MAs(III), while arsW did not. Co-expression of arsV and arsW increased resistance compared with either alone. The cells oxidized methylarsenite and accumulated less methylarsenate. Everted membrane vesicles from E. coli cells expressing arsW-accumulated methylarsenate. We propose that ArsV is a monooxygenase that oxidizes methylarsenite to methylarsenate, which is extruded by ArsW, one of only a few known pentavalent organoarsenical efflux permeases, a novel pathway of organoarsenical resistance. 相似文献
998.
The current study investigated whether women show an attentional bias toward courtship language during the fertile phase of their menstrual cycle. Thirty heterosexual women (17 naturally cycling, 13 using hormonal contraceptives) completed a dichotic listening task on both a high and low fertility day of their menstrual cycle. Participants were asked to verbally repeat (shadow) an emotionally neutral target passage played in one ear while either a neutral or courtship distracter was played in the other ear. Courtship distracters were flirtatious in content but not overtly sexual. Shadowing errors were coded as a measure of attentional bias toward the distracter. Saliva samples were taken to determine whether levels of estradiol, progesterone and/or testosterone correlated with task performance. As predicted, naturally cycling women made more shadowing errors when listening to a courtship distracter during the fertile phase of their cycle than during the nonfertile phase. This effect was moderated by relationship status, such that fertile, mated women showed an attentional bias for courtship language but fertile single women did not. However, because of small sample sizes in the analysis, this relationship should be viewed as preliminary. Hormonal analysis revealed that higher levels of salivary estradiol predicted greater attentional bias toward courtship language in naturally cycling women. These results suggest that women's attention is drawn to verbal courtship signals when they are fertile, and that this shift is linked to increased estradiol release during the periovulatory phase. 相似文献
999.
Amy E. L. Stone Angela Mitchell Jessica Brownell Daniel J. Miklin Lucy Golden-Mason Stephen J. Polyak Michael J. Gale Jr Hugo R. Rosen 《PloS one》2014,9(5)
Plasmacytoid Dendritic Cells (pDCs) represent a key immune cell population in the defense against viruses. pDCs detect viral pathogen associated molecular patterns (PAMPs) through pattern recognition receptors (PRR). PRR/PAMP interactions trigger signaling events that induce interferon (IFN) production to initiate local and systemic responses. pDCs produce Type I and Type III (IFNL) IFNs in response to HCV RNA. Extracellular HCV core protein (Core) is found in the circulation in chronic infection. This study defined how Core modulates PRR signaling in pDCs. Type I and III IFN expression and production following exposure to recombinant Core or β-galactosiade was assessed in human GEN2.2 cells, a pDC cell line. Core suppressed type I and III IFN production in response to TLR agonists and the HCV PAMP agonist of RIG-I. Core suppression of IFN induction was linked with decreased IRF-7 protein levels and increased non-phosphorylated STAT1 protein. Circulating Core protein interferes with PRR signaling by pDCs to suppress IFN production. Strategies to define and target Core effects on pDCs may serve to enhance IFN production and antiviral actions against HCV. 相似文献
1000.