scholarly journals Bmp Induces Osteoblast Differentiation through both Smad4 and mTORC1 Signaling

2016 ◽  
Vol 37 (4) ◽  
Author(s):  
Courtney M. Karner ◽  
Seung-Yon Lee ◽  
Fanxin Long
Keyword(s):  
Protein Synthesis ◽  
Intracellular Signaling ◽  
Osteoblast Differentiation ◽  
De Novo ◽  
Bmp Signaling ◽  
Endoplasmic Reticulum Stress Response ◽  
Versus Protein ◽  
Mtorc1 Signaling ◽  
General Protein Synthesis ◽  
General Protein

ABSTRACT The bone morphogenetic protein (Bmp) family of secreted molecules has been extensively studied in the context of osteoblast differentiation. However, the intracellular signaling cascades that mediate the osteoblastogenic function of Bmp have not been fully elucidated. By profiling mRNA expression in the bone marrow mesenchymal progenitor cell line ST2, we discover that BMP2 induces not only genes commonly associated with ossification and mineralization but also genes important for general protein synthesis. We define the two groups of genes as mineralization related versus protein anabolism signatures of osteoblasts. Although it induces the expression of several Wnt genes, BMP2 activates the osteogenic program largely independently of de novo Wnt secretion. Remarkably, although Smad4 is necessary for the activation of the mineralization-related genes, it is dispensable for BMP2 to induce the protein anabolism signature, which instead critically depends on the transcription factor Atf4. Upstream of Atf4, BMP2 activates mTORC1 to stimulate protein synthesis, resulting in an endoplasmic reticulum stress response mediated by Perk. Thus, Bmp signaling induces osteoblast differentiation through both Smad4- and mTORC1-dependent mechanisms.

scholarly journals Induction of carnitine acetyltransferase by clofibrate in rat liver

1981 ◽  
Vol 194 (1) ◽  
pp. 249-255 ◽  
Author(s):  
B Mittal ◽  
C K R Kurup
Keyword(s):  
Protein Synthesis ◽  
Enzyme Activity ◽  
Rat Liver ◽  
Time Lag ◽  
Mitochondrial Protein ◽  
Carnitine Acetyltransferase ◽  
Enzyme Protein ◽  
General Protein Synthesis ◽  
Liver And Kidney ◽  
General Protein

Administration of the anti-hypercholesterolaemic drug clofibrate to the rat increases the activity of carnitine acetyltransferase (acetyl-CoA-carnitine O-acetyltransferase, EC 2.3.1.7) in liver and kidney. The drug-mediated increase in enzyme activity in hepatic mitochondria shows a time lag during which the activity increases in the microsomal and peroxisomal fractions. The enzyme induced in the particulate fractions is identical with one normally present in mitochondria. The increase in enzyme activity is prevented by inhibitors of RNA and general protein synthesis. Mitochondrial protein-synthetic machinery does not appear to be involved in the process. Immunoprecipitation shows increased concentration of the enzyme protein in hepatic mitochondria isolated from drug-treated animals. In these animals, the rate of synthesis of the enzyme is increased 7-fold.

scholarly journals Proline responding1 Plays a Critical Role in Regulating General Protein Synthesis and the Cell Cycle in Maize

2014 ◽  
Vol 26 (6) ◽  
pp. 2582-2600 ◽  
Author(s):  
Gang Wang ◽  
Jushan Zhang ◽  
Guifeng Wang ◽  
Xiangyu Fan ◽  
Xin Sun ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Critical Role ◽  
General Protein Synthesis ◽  
General Protein

scholarly journals Multiple components of eIF4F are required for protein synthesis-dependent hippocampal long-term potentiation

2013 ◽  
Vol 109 (1) ◽  
pp. 68-76 ◽  
Author(s):  
Charles A. Hoeffer ◽  
Emanuela Santini ◽  
Tao Ma ◽  
Elizabeth C. Arnold ◽  
Ashley M. Whelan ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Synaptic Plasticity ◽  
Translation Initiation ◽  
Translational Control ◽  
Late Phase ◽  
Long Term Potentiation ◽  
Term Potentiation ◽  
General Protein Synthesis ◽  
General Protein

Persistent forms of synaptic plasticity are widely thought to require the synthesis of new proteins. This feature of long-lasting forms of plasticity largely has been demonstrated using inhibitors of general protein synthesis, such as either anisomycin or emetine. However, these drugs, which inhibit elongation, cannot address detailed questions about the regulation of translation initiation, where the majority of translational control occurs. Moreover, general protein synthesis inhibitors cannot distinguish between cap-dependent and cap-independent modes of translation initiation. In the present study, we took advantage of two novel compounds, 4EGI-1 and hippuristanol, each of which targets a different component of the eukaryotic initiation factor (eIF)4F initiation complex, and investigated their effects on long-term potentiation (LTP) at CA3-CA1 synapses in the hippocampus. We found that 4EGI-1 and hippuristanol both attenuated long-lasting late-phase LTP induced by two different stimulation paradigms. We also found that 4EGI-1 and hippuristanol each were capable of blocking the expression of newly synthesized proteins immediately after the induction of late-phase LTP. These new pharmacological tools allow for a more precise dissection of the role played by translational control pathways in synaptic plasticity and demonstrate the importance of multiple aspects of eIF4F in processes underlying hippocampal LTP, laying the foundation for future studies investigating the role of eIF4F in hippocampus-dependent memory processes.

Effects of cycloheximide on thermotolerance expression, heat shock protein synthesis, and heat shock protein mRNA accumulation in rat fibroblasts

1986 ◽  
Vol 6 (4) ◽  
pp. 1088-1094
Author(s):  
R B Widelitz ◽  
B E Magun ◽  
E W Gerner
Keyword(s):  
Protein Synthesis ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Mrna Levels ◽  
Hsp 70 ◽  
Mrna Accumulation ◽  
General Protein Synthesis ◽  
Rat Fibroblasts ◽  
General Protein ◽  
Rat Embryonic Fibroblasts

A single hyperthermic exposure can render cells transiently resistant to subsequent high temperature stresses. Treatment of rat embryonic fibroblasts with cycloheximide for 6 h after a 20-min interval at 45 degrees C inhibits protein synthesis, including heat shock protein (hsp) synthesis, and results in an accumulation of hsp 70 mRNA, but has no effect on subsequent survival responses to 45 degrees C hyperthermia. hsp 70 mRNA levels decreased within 1 h after removal of cycloheximide but then appeared to stabilize during the next 2 h (3 h after drug removal and 9 h after heat shock). hsp 70 mRNA accumulation could be further increased by a second heat shock at 45 degrees C for 20 min 6 h after the first hyperthermic exposure in cycloheximide-treated cells. Both normal protein and hsp synthesis appeared increased during the 6-h interval after hyperthermia in cultures which received two exposures to 45 degrees C for 20 min compared with those which received only one treatment. No increased hsp synthesis was observed in cultures treated with cycloheximide, even though hsp 70 mRNA levels appeared elevated. These data indicate that, although heat shock induces the accumulation of hsp 70 mRNA in both normal and thermotolerant cells, neither general protein synthesis nor hsp synthesis is required during the interval between two hyperthermic stresses for Rat-1 cells to express either thermotolerance (survival resistance) or resistance to heat shock-induced inhibition of protein synthesis.

scholarly journals Effects of cycloheximide on thermotolerance expression, heat shock protein synthesis, and heat shock protein mRNA accumulation in rat fibroblasts.

1986 ◽  
Vol 6 (4) ◽  
pp. 1088-1094 ◽  
Author(s):  
R B Widelitz ◽  
B E Magun ◽  
E W Gerner
Keyword(s):  
Protein Synthesis ◽  
Heat Shock ◽  
Heat Shock Protein ◽  
Mrna Levels ◽  
Hsp 70 ◽  
Mrna Accumulation ◽  
General Protein Synthesis ◽  
Rat Fibroblasts ◽  
General Protein ◽  
Rat Embryonic Fibroblasts

A single hyperthermic exposure can render cells transiently resistant to subsequent high temperature stresses. Treatment of rat embryonic fibroblasts with cycloheximide for 6 h after a 20-min interval at 45 degrees C inhibits protein synthesis, including heat shock protein (hsp) synthesis, and results in an accumulation of hsp 70 mRNA, but has no effect on subsequent survival responses to 45 degrees C hyperthermia. hsp 70 mRNA levels decreased within 1 h after removal of cycloheximide but then appeared to stabilize during the next 2 h (3 h after drug removal and 9 h after heat shock). hsp 70 mRNA accumulation could be further increased by a second heat shock at 45 degrees C for 20 min 6 h after the first hyperthermic exposure in cycloheximide-treated cells. Both normal protein and hsp synthesis appeared increased during the 6-h interval after hyperthermia in cultures which received two exposures to 45 degrees C for 20 min compared with those which received only one treatment. No increased hsp synthesis was observed in cultures treated with cycloheximide, even though hsp 70 mRNA levels appeared elevated. These data indicate that, although heat shock induces the accumulation of hsp 70 mRNA in both normal and thermotolerant cells, neither general protein synthesis nor hsp synthesis is required during the interval between two hyperthermic stresses for Rat-1 cells to express either thermotolerance (survival resistance) or resistance to heat shock-induced inhibition of protein synthesis.

Effect of protein synthesis Inhibition on brain corticotropin-releasing factor and plasma adrenocorticotropin

1990 ◽  
Vol 68 (12) ◽  
pp. 1595-1600
Author(s):  
Daniel A. Haas ◽  
William C. Sturtridge ◽  
Susan R. George
Keyword(s):  
Protein Synthesis ◽  
Corticotropin Releasing Factor ◽  
Protein Synthesis Inhibitor ◽  
Protein Synthesis Inhibition ◽  
Plasma Acth ◽  
Synthesis Inhibitor ◽  
Brain Areas ◽  
Synthesis Inhibition ◽  
General Protein Synthesis ◽  
General Protein

The effect of inhibiting protein synthesis on concentrations of corticotropin-releasing factor (CRF) in rat brain and plasma adrenocorticotropin (ACTH) was assessed following the administration of the general protein synthesis inhibitor anisomycin. Compared with vehicle-injected controls, protein synthesis inhibition resulted in significantly reduced CRF immunoreactivity (CRF-ir) in median eminence within 1 h (p < 0.01), remained decreased after 4 h (p < 0.025), and was nonsignificantly decreased after 24 h. Plasma ACTH levels were greatly increased within 1 h posttreatment (p < 0.0005), continued elevated after 4 h (p < 0.01), and returned to normal levels after 24 h. CRF-ir measured in other brain areas 24 h after anisomycin showed decreased levels in medulla–pons (p < 0.025) and neurointermediate lobe of pituitary (p < 0.05), with no change noted in frontal cortex, hippocampus, midbrain–thalamus, or cerebellum. Overall these data show that blockade of normal protein synthesis with anisomycin can elicit changes in CRF-ir and ACTH content.Key words: corticotropin-releasing factor, adrenocorticotropin, anisomycin.

scholarly journals Biochemical analysis of the stress protein response in human oesophageal epithelium

Gut ◽  
1997 ◽  
Vol 41 (2) ◽  
pp. 156-163 ◽  
Author(s):  
D Hopwood ◽  
S Moitra ◽  
B Vojtesek ◽  
D A Johnston ◽  
J F Dillon ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Heat Shock ◽  
Stress Responses ◽  
Biochemical Analysis ◽  
Ex Vivo ◽  
Stress Protein ◽  
Hsp70 Protein ◽  
Biopsy Specimens ◽  
General Protein Synthesis ◽  
General Protein

Background—The oesophageal epithelium is exposed routinely to noxious agents in the environment, including gastric acid, thermal stress, and chemical toxins. These epithelial cells have presumably evolved effective protective mechanisms to withstand tissue damage and repair injured cells. Heat shock protein or stress protein responses play a central role in protecting distinct cell types from different types of injury.Aim—To determine (i) whether biochemical analysis of stress protein responses in pinch biopsy specimens from human oesophageal epithelium is feasible; (ii) whether undue stresses are imposed on cells by the act of sample collection, thus precluding analysis of stress responses; and (iii) if amenable to experimentation, the type of heat shock protein (Hsp) response that operates in the human oesophageal epithelium.Methods—Tissue from the human oesophagus comprised predominantly of squamous epithelium was acquired within two hours of biopsy and subjected to an in vitro heat shock. Soluble tissue cell lysates derived from untreated or heat shocked samples were examined using denaturing polyacrylamide gel electrophoresis for changes in: (i) the pattern of general protein synthesis by labelling epithelial cells with 35S-methionine and (ii) the levels of soluble Hsp70 protein and related isoforms using immunochemical protein blots.Results—A single pinch biopsy specimen is sufficient to extract and analyse specific sets of polypeptides in the oesophageal epithelium. After ex vivo heat shock, a classic inhibition of general protein synthesis is observed and correlates with the increased synthesis of two major proteins of molecular weight of 60 and 70 kDa. Notably, cells from unheated controls exhibit a “stressed” biochemical state 22 hours after incubation at 37°C, as shown by inhibition of general protein synthesis and increased synthesis of the 70 kDa protein. These data indicate that only freshly acquired specimens are suitable for studying stress responses ex vivo. No evidence was found that the two heat induced polypeptides are previously identified Hsp70 isoforms. In fact, heat shock results in a reduction in the steady state concentrations of Hsp70 protein in the oesophageal epithelium.Conclusion—Systematic and highly controlled studies on protein biochemistry are possible on epithelial biopsy specimens from the human oesophagus. These technical innovations have permitted the discovery of a novel heat shock response operating in the oesophageal epithelium. Notably, two polypeptides were synthesised after heat shock that seem to differ from Hsp70 protein. In addition, the striking reduction in steady state concentrations of Hsp70 protein after heat shock suggests that oesophageal epithelium has evolved an atypical biochemical response to thermal stress.

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