scholarly journals The ALK-2 and ALK-4 activin receptors transduce distinct mesoderm-inducing signals during early Xenopus development but do not co-operate to establish thresholds

Development ◽  
1997 ◽  
Vol 124 (19) ◽  
pp. 3797-3804 ◽  
Author(s):  
N.A. Armes ◽  
J.C. Smith
Keyword(s):  
Cell Types ◽  
Type I ◽  
Cell Stage ◽  
Mesodermal Cell ◽  
Threshold Phenomenon ◽  
Dose Dependent Fashion ◽  
High Concentrations ◽  
Dose Dependent ◽  
Activin Receptors ◽  
Constitutively Active

The TGFbeta family member activin induces different mesodermal cell types in a dose-dependent fashion in the Xenopus animal cap assay. High concentrations of activin induce dorsal and anterior cell types such as notochord and muscle, while low concentrations induce ventral and posterior tissues such as mesenchyme and mesothelium. In this paper we investigate whether this threshold phenomenon involves the differential effects of the two type I activin receptors ALK-2 and ALK-4. Injection of RNA encoding constitutively active forms of the receptors (here designated ALK-2* and ALK-4*) reveals that ALK-4* strongly induces the more posterior mesodermal marker Xbra and the dorsoanterior marker goosecoid in animal cap explants. Maximal levels of Xbra expression are attained using lower concentrations of RNA than are required for the strongest activation of goosecoid, and at the highest doses of ALK-4*, levels of Xbra transcription decrease, as is seen with high concentrations of activin. By contrast, the ALK-2* receptor activates Xbra but fails to induce goosecoid to significant levels. Analysis at later stages reveals that ALK-4* signalling induces the formation of a variety of mesodermal derivatives, including dorsal cell types, in a dose-dependent fashion, and that high levels also induce endoderm. By contrast, the ALK-2* receptor induces only ventral mesodermal markers. Consistent with these observations, ALK-4* is capable of inducing a secondary axis when injected into the ventral side of 32-cell stage embryos whilst ALK-2* cannot. Co-injection of RNAs encoding constitutively active forms of both receptors reveals that ventralising signals from ALK-2* antagonise the dorsal mesoderm-inducing signal derived from ALK-4*, suggesting that the two receptors use distinct and interfering signalling pathways. Together, these results show that although ALK-2* and ALK-4* transduce distinct signals, the threshold responses characteristic of activin cannot be due to interactions between these two pathways; rather, thresholds can be established by ALK-4* alone. Furthermore, the effects of ALK-2* signalling are at odds with it behaving as an activin receptor in the early Xenopus embryo.

Surrogate light chain expression beyond the pre-B cell stage promotes tolerance in a dose-dependent fashion

2015 ◽  
Vol 57 ◽  
pp. 30-41 ◽  
Author(s):  
Laurens P. Kil ◽  
Odilia B.J. Corneth ◽  
Marjolein J.W. de Bruijn ◽  
Patrick S. Asmawidjaja ◽  
Arndt Krause ◽  
...  
Keyword(s):  
B Cell ◽  
Light Chain ◽  
Cell Stage ◽  
Surrogate Light Chain ◽  
Dose Dependent Fashion ◽  
Dose Dependent

Evidence for a potential role of glucagon during eye growth regulation in chicks

2002 ◽  
Vol 19 (6) ◽  
pp. 755-766 ◽  
Author(s):  
MARITA P. FELDKAEMPER ◽  
FRANK SCHAEFFEL
Keyword(s):  
Visual Processing ◽  
Growth Regulation ◽  
Amacrine Cells ◽  
Early Gene ◽  
Eye Growth ◽  
Dose Dependent Fashion ◽  
High Concentrations ◽  
Dose Dependent ◽  
Glucagon Antagonist

Eye growth and refraction are regulated by visual processing in the retina. Until now, the messengers released by the retina to induce these changes are largely unknown. Previously, it was found that glucagon amacrine cells respond to defocus in the retinal image and even to its sign. The expression of the immediate-early gene product ZENK increased in this cell population in eyes wearing plus lenses and decreased in minus lens-treated chicks. Moreover, it was shown that the amount of retinal glucagon mRNA increased during treatment with positive lenses. Therefore, it seems likely that these cells contribute to the visual regulation of ocular growth and that glucagon may act as a stop signal for eye growth. The purpose of the present study was to accumulate further evidence for a role of glucagon in the visual control of eye growth. Chicks were treated with plus and minus lenses after injection of different amounts of the glucagon antagonist des-His1-Glu9-glucagon-amide or the agonist Lys17,18,Glu21-glucagon, respectively. Refractive development and eye growth were recorded by automated infrared photorefraction and A-scan ultrasound, respectively. The glucagon antagonist inhibited hyperopia development, albeit only in a narrow concentration range, and at most by 50%, but not myopia development. In contrast, the agonist inhibited myopia development in a dose-dependent fashion. At high concentrations, it also prevented hyperopia development.

scholarly journals Regulatory Roles of Bone Morphogenetic Proteins and Glucocorticoids in Catecholamine Production by Rat Pheochromocytoma Cells

Endocrinology ◽  
2005 ◽  
Vol 146 (12) ◽  
pp. 5332-5340 ◽  
Author(s):  
Yoshihiro Kano ◽  
Fumio Otsuka ◽  
Masaya Takeda ◽  
Jiro Suzuki ◽  
Kenichi Inagaki ◽  
...  
Keyword(s):  
Tyrosine Hydroxylase ◽  
Pc12 Cells ◽  
Bone Morphogenetic Proteins ◽  
Bmp Signaling ◽  
Type I ◽  
Dependent Manner ◽  
Catecholamine Synthesis ◽  
Pheochromocytoma Cells ◽  
Dose Dependent Fashion ◽  
Dose Dependent

We here report a new physiological system that governs catecholamine synthesis involving bone morphogenetic proteins (BMPs) and activin in the rat pheochromocytoma cell line, PC12. BMP type I receptors, including activin receptor-like kinase-2 (ALK-2) (also referred to as ActRIA) and ALK-3 (BMPRIA), both type II receptors, ActRII and BMPRII, as well as the ligands BMP-2, -4, and -7 and inhibin/activin subunits were expressed in PC12 cells. PC12 cells predominantly secrete dopamine, whereas noradrenaline and adrenaline production is negligible. BMP-2, -4, -6, and -7 and activin A each suppressed dopamine and cAMP synthesis in a dose-dependent fashion. The BMP ligands also decreased 3,4-dihydroxyphenylalanine decarboxylase mRNA expression, whereas activin suppressed tyrosine hydroxylase expression. BMPs induced both Smad1/5/8 phosphorylation and Tlx2-Luc activation, whereas activin stimulated 3TP-Luc activity and p38 MAPK phosphorylation. ERK signaling was not affected by BMPs or activin. Dexamethasone enhanced catecholamine synthesis, accompanying increases in tyrosine hydroxylase and 3,4-dihydroxyphenylalanine decarboxylase transcription without cAMP accumulation. In the presence of dexamethasone, BMPs and activin failed to reduce dopamine as well as cAMP production. In addition, dexamethasone modulated mitotic suppression of PC12 induced by BMPs in a ligand-dependent manner. Furthermore, intracellular BMP signaling was markedly suppressed by dexamethasone treatment and the expression of ALK-2, ALK-3, and BMPRII was significantly inhibited by dexamethasone. Collectively, the endogenous BMP/activin system plays a key role in the regulation of catecholamine production. Controlling activity of the BMP system may be critical for glucocorticoid-induced catecholamine synthesis by adrenomedullar cells.

Effects of Ryo-Kan-Kyomi-Sin-Ge-Nin-To Extract on Degranulation of and Histamine Release from Rat Mast Cells

1991 ◽  
Vol 19 (03n04) ◽  
pp. 243-249 ◽  
Author(s):  
Tadayoshi Shibata ◽  
Takeshi Kono ◽  
Tsukasa Tanii ◽  
Nobuyuki Mizuno ◽  
Toshio Hamada
Keyword(s):  
Mast Cells ◽  
Histamine Release ◽  
Type I ◽  
Type I Allergy ◽  
Dose Dependent Fashion ◽  
China And Japan ◽  
Dose Dependent ◽  
Rat Mast Cells

The effects of Ryo-kan-kyomi-sin-ge-nin-to (RKSG) extract, a medicinal agent traditionally used in China and Japan for treatment of asthma, on the degranulation of and histamine release from rat mast cells were studied. At a concentration of 5 mg/ml RKSG, degranulation of mast cells stimulated either by antigen (DNP-Ascaris) or compound 48/80 was markedly suppressed. At a concentration of 1-5 mg/ml RKSG, histamine release from mast cells due to application of either antigen or compound 48/80 was inhibited in a dose-dependent fashion. These results suggest that RKSG may be useful for the treatment of type I allergy-related diseases.

Regulation of digestion. II. Effects of insulin and glucagon on pancreatic secretion

1984 ◽  
Vol 246 (4) ◽  
pp. G451-G456
Author(s):  
H. C. Tseng ◽  
J. H. Grendell ◽  
S. S. Rothman
Keyword(s):  
Exocrine Pancreas ◽  
Digestive Enzyme ◽  
Celiac Artery ◽  
Portal Circulation ◽  
Amylase Output ◽  
Endocrine Hormones ◽  
Dose Dependent Fashion ◽  
High Concentrations ◽  
Dose Dependent ◽  
Islet Cell Hormones

The endocrine islet-cell hormones insulin and glucagon are secreted at high concentrations into an intrapancreatic portal circulation and have been reported to affect the secretion of digestive enzyme by the exocrine pancreas. In the present experiments, insulin and glucagon were injected into the celiac artery of anesthetized rats to evaluate their effects on the secretion of amylase and trypsinogen by the pancreas. Neither hormone when given alone significantly changed the output of either enzyme. However, when given with the pancreatic secretagogue cholecystokinin, each altered the effect of injection of cholecystokinin. In a dose-dependent fashion insulin increased trypsinogen output without affecting amylase output, whereas glucagon inhibited amylase output and left trypsinogen output unchanged. Thus, both hormones produced a more trypsinogen-dominant pancreatic juice than that observed with cholecystokinin alone, although in different ways. These findings suggest that the endocrine hormones insulin and glucagon may regulate secretion of digestive enzymes by the pancreas by modulating the response to stimuli of overall protein secretion such as cholecystokinin.

scholarly journals Enterotoxicity and Cytotoxicity of Vibrio parahaemolyticus Thermostable Direct Hemolysin in In Vitro Systems

2000 ◽  
Vol 68 (6) ◽  
pp. 3180-3185 ◽  
Author(s):  
Francesco Raimondi ◽  
Joseph P. Y. Kao ◽  
Carla Fiorentini ◽  
Alessia Fabbri ◽  
Gianfranco Donelli ◽  
...  
Keyword(s):  
Vibrio Parahaemolyticus ◽  
Fluid Secretion ◽  
Cell Types ◽  
Chloride Secretion ◽  
Free Calcium ◽  
Thermostable Direct Hemolysin ◽  
High Concentrations ◽  
Intestinal Fluid Secretion ◽  
Dose Dependent

ABSTRACT Vibrio parahaemolyticus is a marine bacterium known to be a common cause of seafood gastroenteritis worldwide. The thermostable direct hemolysin (TDH) has been proposed to be a major virulence factor of V. parahaemolyticus. TDH causes intestinal fluid secretion as well as cytotoxicity in a variety of cell types. In this study, we investigated the interplay between the hemolysin's enterotoxic and cytotoxic effects by using both human and rat cell monolayers. As revealed by microspectrofluorimetry, the toxin causes a dose-dependent increase in intracellular free calcium in both Caco-2 and IEC-6 cells. This effect was reversible only when low toxin concentrations were tested. The TDH-activated ion influx pathway is not selective for calcium but admits ions such sodium and manganese as well. Furthermore, in the same range of concentration, the hemolysin triggers a calcium-dependent chloride secretion. At high concentrations, TDH induces a dose-dependent but calcium-independent cell death as assessed by functional, biochemical, and morphological assays.

ORP-3, a human oxysterol-binding protein gene differentially expressed in hematopoietic cells

Blood ◽  
2001 ◽  
Vol 98 (7) ◽  
pp. 2279-2281 ◽  
Author(s):  
Claudia C. Gregorio-King ◽  
Gregory R. Collier ◽  
Janine S. McMillan ◽  
Caryll M. Waugh ◽  
Janet L. McLeod ◽  
...  
Keyword(s):  
Binding Protein ◽  
Cholesterol Biosynthesis ◽  
Hematopoietic Cells ◽  
Cell Types ◽  
Oxysterol Binding Protein ◽  
Cd34 Cells ◽  
Proliferation And Differentiation ◽  
Dose Dependent Fashion ◽  
High Degree ◽  
Dose Dependent

Using differential display polymerase chain reaction, a gene was identified in CD34+-enriched populations that had with low or absent expression in CD34− populations. The full coding sequence of this transcript was obtained, and the predicted protein has a high degree of homology to oxysterol-binding protein. This gene has been designated OSBP-related protein 3 (ORP-3). Expression of ORP-3 was found to be 3- to 4-fold higher in CD34+ cells than in CD34− cells. Additionally, expression of this gene was 2-fold higher in the more primitive subfraction of hematopoietic cells defined by the CD34+38− phenotype and was down-regulated with the proliferation and differentiation of CD34+ cells. The ORP-3 predicted protein contains an oxysterol-binding domain. Well-characterized proteins expressing this domain bind oxysterols in a dose-dependent fashion. Biologic activities of oxysterols include inhibition of cholesterol biosynthesis and cell proliferation in a variety of cell types, among them hematopoietic cells. Characterization and differential expression of ORP-3 implicates a possible role in the mediation of oxysterol effects on hematopoiesis.

scholarly journals The effects of diphosphonates on the growth and glycolysis of connective-tissue cells in culture

1978 ◽  
Vol 172 (1) ◽  
pp. 97-107 ◽  
Author(s):  
D K Fast ◽  
R Felix ◽  
C Dowse ◽  
W F Neuman ◽  
H Fleisch
Keyword(s):  
Cell Types ◽  
Detectable Effect ◽  
Skin Cells ◽  
N2 Atmosphere ◽  
Dose Dependent Fashion ◽  
Cartilage Cells ◽  
Ear Cartilage ◽  
Drug Doses ◽  
Dose Dependent

1. The effects of two diphosphonates (compounds containing a P-C-P bond), disodium dichloromethanediphosphonate and disodium 1-hydroxyethane-1,1-diphosphonate, on the metabolism of cultured rat calvaria cells, rabbit ear cartilage cells and rat skin fibroblasts were investigated. 2. The diphosphonates had no effect on the growth of cartilage cells and on the exponential growth of the calvaria cells and the fibroblasts. However, dichloromethanediphosphonate stopped the growth of the calvaria cells and the fibroblasts after the beginning of confluence, whereas the untreated cells were still growing to a certain extent. This inhibition was dose-dependent. After the drug was withdrawn, the cells recovered slowly. 1-Hydroxyethane-1,1-diphosphonate had no detectable effect on the growth of any of the cell types studied. Both diphosphonates decreased the cloning efficiency of calvaria cells and fibroblasts. 3. The K+ content of cartilage, calvaria and skin cells was diminished only by the highest (0.25 mM) concentration of dichloromethanediphosphonate. 4. Radioactive dichloromethanediphosphonate and 1-hydroxyethane-1,1-diphosphonate were taken up linearly with time for at least 48 h by calvaria cells and fibroblasts. The diphosphonate concentration in the cells depended on its concentration in the medium. 5. Both diphosphonates, in a dose-dependent fashion, markedly inhibited glycolysis, dichloromethanediphosphonate being more effective than 1-hydroxyethane-1,1-diphosphonate, at drug doses that had no effect on cell growth or cellular K+ content. Calvaria cells were much more sensitive than cartilage cells. When cartilage cells were cultured in an N2 atmosphere, these effects on glucose and lactate metabolism disappeared. 6. As increased acid production appears to be associated with resorption of bone, this decrease in lactate may explain why diphosphonates are effective inhibitors of bone resorption in vivo.

scholarly journals A common pattern of DNase-I footprinting throughout the human mtDNA unveils clues for a chromatin-like organization

2017 ◽  
Author(s):  
Amit Blumberg ◽  
Charles G. Danko ◽  
Anshul Kundaje ◽  
Dan Mishmar
Keyword(s):  
Cell Types ◽  
Regulatory Elements ◽  
Dnase I ◽  
Sequence Specificity ◽  
Physiological Importance ◽  
Dnase I Footprinting ◽  
Dose Dependent Fashion ◽  
Dna Organization ◽  
First Time ◽  
Dose Dependent

AbstractHuman mitochondrial DNA (mtDNA) is believed to lack chromatin and histones. Instead, it is coated solely by the transcription factor TFAM, which binds the mtDNA without sequence specificity and packs it into a bacterial-like nucleoid in a dose-dependent fashion. We asked whether mtDNA packaging is more regulated than once thought. As a first step to address this question, we analyzed mtDNA DNase-I-seq experiments in 324 different human cell types and found, for the first time, a pattern of 29 Genomic footprinting (DGF) sites throughout the mtDNA shared by ∼90% of the tested samples. Low SNP density at the DGF sites, and their conservation in mouse DNase-seq experiments, reflect strong selective constraints. Co-localization of the DGFs with known mtDNA regulatory elements and with recently-discovered transcription pausing sites, suggest a role for such DGFs in mtDNA transcription. Altered mtDNA DGF pattern in IL-3 treated CD+34 cells offer first clue to their physiological importance. Taken together, human mtDNA has a conserved and regulated protein-DNA organization, which is likely involved in regulation of mtDNA gene expression.

scholarly journals Genome-Encoded Cytoplasmic Double-Stranded RNAs, Found in C9ORF72 ALS-FTD Brain, Provoke Propagated Neuronal Death

2018 ◽  
Author(s):  
Steven Rodriguez ◽  
Benjamin R. Schrank ◽  
Asli Sahin ◽  
Hawra Al-Lawati ◽  
Isabel Costantino ◽  
...  
Keyword(s):  
Neuronal Death ◽  
Neural Circuit ◽  
Cell Types ◽  
Type I ◽  
Dependent Manner ◽  
Molecular Pattern ◽  
Innate Immune Signaling ◽  
Human Neurons ◽  
Signaling Activation ◽  
Dose Dependent

SUMMARYInnate immune signaling activation and DNA damage are pathological hallmarks of aging that may herald multiple adult-onset neurodegenerative diseases. Here, we report that both cell autonomous and non-autonomous neuronal death are triggered by the production of cytoplasmic double-stranded RNA (cdsRNA) from a regulated, disarticulated transgene in the setting of type I interferon (IFN-I) signaling. CdsRNA is a pathogen associated molecular pattern that induces IFN-I in many cell types. Transfection of a dsRNA mimetic into cultured human neurons also induces IFN-I signaling and cell death in a dose-dependent manner. Direct relevance to human disease is found in neurons of ALS-FTD patients carrying C9ORF72 intronic hexanucleotide expansions; cdsRNA isolated from these tissues is comprised of repeat sequences. Together, these findings implicate cdsRNA generated from genomic sequences in neurons as a trigger for sterile, viral-mimetic IFN-I induction and propagated neuronal death within in a neural circuit in the aging nervous system.

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