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Synthesis Inhibitor Cycloheximide (synthesis + inhibitor_cycloheximide)

Distribution by Scientific Domains
Life Sciences75%

Kinds of Synthesis Inhibitor Cycloheximide

  • protein synthesis inhibitor cycloheximide
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    Selected Abstracts

    Regulated expression of syndecan-4 in rat calvaria osteoblasts induced by fibroblast growth factor-2

    JOURNAL OF CELLULAR BIOCHEMISTRY, Issue 2 2007
    Shu Jun Song
    Abstract Fibroblast growth factor-2 (FGF2) is a member of a prominent growth factor family that drives proliferation in a wide variety of cell types, including osteoblasts. The binding and signal transduction triggered by these mitogens is dependent on glycosaminoglycan (GAG) sugars, particularly of the heparan sulfate (HS) class. These are secreted in proteoglycan (PG) complexes, some of which become FGF co-receptors. The syndecans, the transmembrane forms of HSPG of which there are four members, act as multifunctional receptors for a variety of ligands involved in cell-extracellular matrix (ECM) adhesion as well as growth factor binding. To understand the role of syndecans in developing osteoblasts, the effects of exogenous FGF2 on syndecan expression were examined using primary rat calvarial osteoblasts. All four syndecan mRNAs were expressed in the osteoblasts, although only syndecan-4 was upregulated by FGF2 treatment in a dose-dependent manner. This upregulation could be abrogated by pretreatment with the protein synthesis inhibitor cycloheximide, suggesting that the upregulation of syndecan-4 by FGF2 is not a primary response. Osteoblast proliferation and mineralization were enhanced by exogenous FGF2 treatment, but could be specifically diminished by anti-syndecan-4 antibody pretreatment. This treatment also blocked FGF2-induced extracellular signal-regulated kinase activation, but not the expression of the bone-specific transcription factor Runx2. These results demonstrate that mitogen-triggered syndecan-4 expression is an intrinsic part of the pathways subtending osteoblast proliferation and mineralization. J. Cell. Biochem. 100: 402,411, 2007. © 2006 Wiley-Liss, Inc. [source]

    Reduction of intracellular pH inhibits constitutive expression of Cyclooxygenase-2 in human colon cancer cells

    JOURNAL OF CELLULAR PHYSIOLOGY, Issue 2 2004
    Daniela Pirkebner
    Cyclooxygenase-2 (COX-2) over-expression is critically involved in tumor formation. Intracellular pH (pHi) has been shown to be alkaline in cancer cells, and to be an important trigger for cell proliferation. This study therefore analyzed the relationship between pHi and COX-2 expression. HRT-18 and Caco-2 cells cultured in medium with bicarbonate maintained a pHi of ,7.6, which is higher than that of non-neoplastic cells. Cells grown in bicarbonate-free medium with a pH at 6.8 showed a reduction in pHi to approximately 7.0. Importantly, reduction of pHi resulted in a complete inhibition of COX-2 mRNA and protein expression. When cells were grown in bicarbonate-supplemented medium at pH 6.8, pHi maintained at ,7.6 and COX-2 expression was not inhibited. Additionally, analysis utilizing protein synthesis inhibitor cycloheximide demonstrated that pHi mediated inhibition of COX-2 mRNA expression requires de novo protein synthesis of regulatory protein(s). These data strongly suggest that an alkaline pHi is an important trigger for constitutive COX-2 expression. Defining pHi -mediated mechanisms that govern the constitutive COX-2 expression may help in developing new strategies to block COX-2 over-expression in cancer cells. J. Cell. Physiol. 198: 295,301, 2004© 2003 Wiley-Liss, Inc. [source]

    Modulation of Na+ -H+ exchange isoforms NHE1 and NHE3 by insulin-like growth factor-1 in isolated bovine articular chondrocytes

    JOURNAL OF ORTHOPAEDIC RESEARCH, Issue 11 2008
    Amanda L. Tattersall
    Abstract Incubation with serum modulates the transporters that regulate intracellular pH (pHi) in articular chondrocytes, upregulating acid extrusion by Na+ -H+ exchange (NHE). There is stimulation of NHE1, together with induction of NHE3 activity. These isoforms exhibit differential responses to components of mechanical load experienced by chondrocytes during joint loading. The identity of the component(s) of serum responsible is unknown. A possibility, however, is insulin-like growth factor-1 (IGF-1), present in normal cartilage and found at enhanced levels in osteoarthritic tissue. In the present study, the effects of IGF-1 on pHi regulation have been characterized using fluorescence measurements of bovine articular chondrocytes, and the sensitivity of pHi regulation to hyperosmotic shock and raised hydrostatic pressure determined. For cells isolated in the absence of IGF-1, pHi recovery following acidification was predominantly mediated by NHE1. Recovery was enhanced when cells were incubated for 18 h with 20 ng mL,1 IGF; this effect represented increased acid extrusion by NHE1, supplemented by NHE3 activity. NHE3 activity was not detected in IGF-1-treated cells that had been incubated with the protein synthesis inhibitor cycloheximide, although NHE1 activity was unaffected. In the absence of IGF-1, suspension in hyperosmotic solutions or raised hydrostatic pressure enhanced pHi recovery of acidified cells. This response was missing in cells incubated with IGF-1. Unresponsiveness to hyperosmotic shock represented inhibition of NHE3 activity, and was prevented using the protein kinase A inhibitor KT5720. For raised hydrostatic pressure, a decrease in NHE1 activity was responsible, and was prevented by the protein kinase C inhibitor chelerythrine. © 2008 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 26:1428,1433, 2008 [source]

    Mechanisms of 17 ,-oestradiol induced vasodilatation in isolated pressurized rat small arteries

    BRITISH JOURNAL OF PHARMACOLOGY, Issue 3 2000
    Linda Shaw
    The influence of 17 ,-oestradiol on pressurized isolated rat mesenteric and coronary small arteries was investigated. 17 ,-oestradiol caused rapid (t1.0<5 mins) concentration-dependent relaxations of pre-contracted pressurized (50 mmHg) isolated rat mesenteric and coronary arteries. Similar responses were observed in both vessel types. Significant relaxations were only observed at concentrations exceeding 3 ,M. The vasodilatory responses in both types of artery were unaffected by 10 ,ML -nitro arginine (L -NNA) alone or in the presence of 10 ,M indomethacin, inhibitors of nitric oxide and prostaglandin synthesis respectively. They were also unaffected by the pre-contracting agent used i.e. high K+ or U46619 (a thromboxane analogue). Neither the oestrogen receptor antagonist ICI 182,780 (10 ,M) nor the protein synthesis inhibitor cycloheximide (100 ,M) had any effect on the responses of mesenteric arteries to 17 ,-oestradiol. 17 ,-oestradiol had only a minor effect on mesenteric arterial diameter over a concentration range similar to the effective vasodilatory range for 17 ,-oestradiol. Membrane impermeant 17 ,-oestradiol conjugated to bovine serum albumin (,-oestradiol-17hemisuccinate-BSA) (E-H-BSA) resulted in a vasodilatation of pressurized arteries. Wortmannin, an inhibitor of myosin light chain kinase, near maximally relaxed pressurized mesenteric arteries although the time course for the response was significantly slower than that for 17 ,-oestradiol. These results taken together suggest that the acute effects of 17 ,-oestradiol on isolated pressurized arterial tone may be due to effects directly on the vascular smooth muscle via non-genomic mechanisms that involve a stereospecific interaction at the plasma membrane. British Journal of Pharmacology (2000) 129, 555,565; doi:10.1038/sj.bjp.0703084 [source]