scholarly journals Antenatal betamethasone increases vascular reactivity to endothelin-1 by upregulation of CD38/cADPR signaling

2014 ◽  
Vol 5 (1) ◽  
pp. 56-62 ◽  
Author(s):  
J.-H. Lee ◽  
J. Zhang ◽  
G. A. Massmann ◽  
J. P. Figueroa
Keyword(s):  
Vascular Reactivity ◽  
Adult Life ◽  
Adenosine Diphosphate ◽  
Adp Ribosyl Cyclase ◽  
Antenatal Steroids ◽  
Pregnant Sheep ◽  
Antenatal Steroid ◽  
Increased Sensitivity ◽  
Cyclic Adenosine Diphosphate

Antenatal steroid administration is associated with hypertension in adult life; however, the mechanisms underlying this phenomenon are unclear. The aim of this study was to further characterize the effects of antenatal glucocorticoid exposure on the endothelin (ET-1) system, specifically to ascertain the role of the cyclic adenosine diphosphate ribose (cADPR)/ryanodine receptor pathway in the increased sensitivity to ET-1 observed in the offspring exposed to antenatal glucocorticoids. Pregnant sheep were randomly treated with betamethasone (Beta; 0.17 mg/kg) or vehicle at 80 and 81 days of gestation. In adults, we studied endothelium-denuded arterial segments of the brachial arteries. ET-1-induced vasoconstriction was significantly higher in the arteries from Beta sheep (F=3.5, P<0.05). Inhibition of ADP-ribosyl cyclase with 2-2'-dihydroxy-azobenzene significantly decreased the ET-1-induced contraction in Beta but not in vehicle-treated sheep. Nicotinamide attenuated ET-1 contraction in both, but it was significantly more pronounced in the Beta-treated sheep. No significant differences were observed following KCl-induced (6.25–75 mM) contraction. Nicotinamide (10 mM) significantly attenuated the KCl-induced vasoconstriction in both groups. In KCl (62.5 mM)-constricted arteries, the effect of nicotinamide (NIC) was significantly greater in the vehicle-treated sheep (50% relaxation v. 40% relaxation; t=2.2, P<0.05). In contrast, the sodium nitroprusside (SNP) relaxation was not statistically different. An additive effect was observed when NIC and SNP were used in combination and it was also more pronounced in vehicle-treated sheep. We conclude that the increased response to ET-1 is mediated by activation of the CD38/cADPR signaling pathway. Further studies are required to identify the effectors downstream from cADPR affected by exposure to antenatal steroids.

Role of endothelium-derived relaxing factors in the renal response to vasoactive agents in hypothyroid rats

2003 ◽  
Vol 285 (1) ◽  
pp. E182-E188 ◽  
Author(s):  
Juan Manuel Moreno ◽  
Rosemary Wangensteen ◽  
Juan Sainz ◽  
Isabel Rodríguez-Gomez ◽  
Virginia Chamorro ◽  
...  
Keyword(s):  
Vascular Reactivity ◽  
Ang Ii ◽  
Vasoactive Agents ◽  
Normal Response ◽  
No Donor ◽  
Increased Sensitivity ◽  
Renal Vascular ◽  
And Control ◽  
Renal Responses

This study analyzed the role of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in the abnormal renal vascular reactivity of hypothyroid rats. Renal responses to vasoconstrictors [VC: phenylephrine (PHE) and ANG II] and vasodilators [VD: ACh, sodium nitroprusside (SNP), and papaverine (PV)] were studied in kidneys from control and hypothyroid rats under normal conditions and after NO or EDHF blockade. NO was blocked by the administration of Nω-nitro-l-arginine methyl ester (l-NAME) and EDHF by the administration of tetraethylammonium (TEA) or by an increased extracellular K+. The response to VC was also evaluated after endothelium removal. Hypothyroid kidneys showed reduced responsiveness to PHE and a normal response to ANG II. l-NAME and TEA administration produced an increased sensitivity to PHE and to ANG II in control preparations. l-NAME also increased the response to PHE in hypothyroid kidneys, but the differences between control and hypothyroid kidneys were maintained. TEA administration did not change the response to either VC in hypothyroid preparations. In endothelium-removed preparations, TEA was unable to increase pressor responsiveness to VC. Hypothyroid kidneys showed reduced responsiveness to ACh and SNP and normal response to PV. The differences between hypothyroid and control preparations in the responses to ACh and SNP were maintained after l-NAME or increased K+. In conclusion, this study shows that 1) the attenuated response to PHE in hypothyroidism is not related to an increased production of endothelium-derived relaxing factors NO and EDHF; 2) the response to VC in hypothyroid preparations is insensitive to EDHF blockade; and 3) hypothyroid preparations have a reduced reactivity to the NO donor, and NO-independent vasodilatation remains unaffected.

CD157 is an important mediator of neutrophil adhesion and migration

Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 4269-4278 ◽  
Author(s):  
Ada Funaro ◽  
Erika Ortolan ◽  
Bruna Ferranti ◽  
Lucia Gargiulo ◽  
Rosario Notaro ◽  
...  
Keyword(s):  
Cell Shape ◽  
Adenosine Diphosphate ◽  
Enzymatic Activities ◽  
Matrix Proteins ◽  
Β2 Integrin ◽  
Important Mediator ◽  
Adp Ribosyl Cyclase ◽  
And Migration ◽  
Cyclic Adenosine Diphosphate

Abstract CD157, a glycosylphosphatidylinositol (GPI)–anchored protein encoded by a member of the CD38 NADase/ADP-ribosyl cyclase gene family, is expressed on the surface of most human circulating neutrophils. This work demonstrates that CD157 is a receptor that induces reorganization of the cytoskeleton and significant changes in cell shape, and that signals mediated by CD157 act through modulation of cytosolic Ca2+ concentration. These signals are independent of the products of CD157's enzymatic activities (ie, cyclic adenosine diphosphate [ADP]–ribose and ADP-ribose). Indeed, the enzymatic activities of CD157 in circulating neutrophils as well as in dimethyl sulfoxide (DMSO)–differentiated (CD157+/CD38-) HL-60 cells, are hardly detectable. This work also shows that the receptorial activity relies on cross-talk between CD157 and β2 integrin. CD157 localizes in GM1-enriched lipid rafts and, upon activation, it migrates to the uropod, a structure specialized in motility and adhesive functions. Indeed, CD157 is involved in adhesion to extracellular matrix proteins and in chemotaxis induced in vitro by formyl-methionyl-leucyl-phenylalanine (fMLP). These findings were consistent with the results obtained in neutrophils from patients with paroxysmal nocturnal hemoglobinuria (PNH), in which CD157 is deficient. These neutrophils showed constant defects in adhesion and migration. Our data attribute specific and crucial roles to CD157 in the regulation of innate immunity during inflammation.

Haemostatic Platelet Plug Formation in the Isolated Rabbit Mesenteric Preparation - An Analysis of Red Blood Cell Participation

1980 ◽  
Vol 44 (01) ◽  
pp. 006-008 ◽  
Author(s):  
D Bergqvist ◽  
K-E Arfors
Keyword(s):  
Whole Blood ◽  
Platelet Rich Plasma ◽  
Adenosine Diphosphate ◽  
In Vitro Test ◽  
Pharmacological Agents ◽  
Vitro Test ◽  
Releasing Effect ◽  
Plug Formation

SummaryIn a model using an isolated rabbit mesenteric preparation microvessels were transected and the time until haemostatic plugs formed was registered. Perfusion of platelet rich plasma gave no haemostasis whereas whole blood did. Addition of chlorpromazine or adenosine to the whole blood significantly prolonged the time for haemostasis, and addition of ADP to the platelet rich plasma significantly shortened it. It is concluded that red cells are necessary for a normal haemostasis in this model, probably by a combination of a haemodynamic and ADP releasing effect.The fundamental role of platelets in haemostatic plug formation is unquestionable but there are still problems concerning the stimulus for this process to start. Three platelet aggregating substances have been discussed – thrombin, adenosine diphosphate (ADP) and collagen. Evidence speaking in favour of thrombin is, however, very minimal, and the discussion has to be focused on collagen and ADP. In an in vitro system using polyethylene tubings we have shown that "haemostasis" can be obtained without the presence of collagen but against these results can be argued that it is only another in vitro test for platelet aggregation (1).To be able to induce haemostasis in this model, however, the presence of red blood cells is necessary. To further study this problem we have developed a model where haemostatic plug formation can be studied in the isolated rabbit mesentery and we have briefly reported on this (2).Thus, it is possible to perfuse the vessels with whole blood as well as with platelet rich plasma (PRP) and different pharmacological agents of importance.

Platelet Aggregation in Whole Blood: The Role of Thromboxane A2 and Adenosine Diphosphate

1985 ◽  
Vol 54 (03) ◽  
pp. 612-616 ◽  
Author(s):  
A J Carter ◽  
S Heptinstall
Keyword(s):  
Platelet Aggregation ◽  
Whole Blood ◽  
Adenosine Diphosphate ◽  
Blood Platelet ◽  
Thromboxane B2 ◽  
Lipoxygenase Inhibitor ◽  
Thromboxane Synthase Inhibitor ◽  
Synthase Inhibitor

SummaryThe platelet aggregation that occurred in whole blood in response to several aggregating agents (collagen, arachidonic acid, adenosine diphosphate, adrenaline and thrombin) was measured using an Ultra-Flo 100 Whole Blood Platelet Counter. The amounts of thromboxane B2 produced were measured by radioimmunoassay. The effects of various inhibitors of thromboxane synthesis and the effects of apyrase, an enzyme that destroys adenosine diphosphate, were determined.Platelet aggregation was always accompanied by the production of thromboxane B2, and the amounts produced depended on the nature and concentration of the aggregating agent used. The various inhibitors of thromboxane synthesis - aspirin and flurbiprofen (cyclo-oxygenase inhibitors), BW755C (a cyclo-oxygenase and lipoxygenase inhibitor) and dazoxiben (a selective thromboxane synthase inhibitor) - did not markedly inhibit aggregation. Results obtained using apyrase showed that adenosine diphosphate contributed to the aggregation process, and that its role must be acknowledged when devising means of inhibiting platelet aggregation in vivo.

Collagen-Induced Platelet Aggregation: -Evidence Against the Essential Role of Platelet Adenosine Diphosphate

1979 ◽  
Vol 42 (04) ◽  
pp. 1193-1206 ◽  
Author(s):  
Barbara Nunn
Keyword(s):  
Platelet Aggregation ◽  
Time Course ◽  
Essential Role ◽  
Atp Release ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
High Doses ◽  
Induced Aggregation

SummaryThe hypothesis that platelet ADP is responsible for collagen-induced aggregation has been re-examined. It was found that the concentration of ADP obtaining in human PRP at the onset of aggregation was not sufficient to account for that aggregation. Furthermore, the time-course of collagen-induced release in human PRP was the same as that in sheep PRP where ADP does not cause release. These findings are not consistent with claims that ADP alone perpetuates a collagen-initiated release-aggregation-release sequence. The effects of high doses of collagen, which released 4-5 μM ADP, were not inhibited by 500 pM adenosine, a concentration that greatly reduced the effect of 300 μM ADP. Collagen caused aggregation in ADP-refractory PRP and in platelet suspensions unresponsive to 1 mM ADP. Thus human platelets can aggregate in response to collagen under circumstances in which they cannot respond to ADP. Apyrase inhibited aggregation and ATP release in platelet suspensions but not in human PRP. Evidence is presented that the means currently used to examine the role of ADP in aggregation require investigation.

scholarly journals An R2R3-type myeloblastosis transcription factor MYB103 is involved in phosphorus remobilization

2020 ◽  
Vol 2 (1) ◽  
Author(s):  
Fangwei Yu ◽  
Shenyun Wang ◽  
Wei Zhang ◽  
Hong Wang ◽  
Li Yu ◽  
...  
Keyword(s):  
Cell Wall ◽  
Transcription Factor ◽  
Abiotic Stresses ◽  
Myb Transcription Factor ◽  
Ethylene Signaling ◽  
Biotic And Abiotic Stresses ◽  
P Deficiency ◽  
P Concentration ◽  
Increased Sensitivity

Abstract The members of myeloblastosis transcription factor (MYB TF) family are involved in the regulation of biotic and abiotic stresses in plants. However, the role of MYB TF in phosphorus remobilization remains largely unexplored. In the present study, we show that an R2R3 type MYB transcription factor, MYB103, is involved in phosphorus (P) remobilization. MYB103 was remarkably induced by P deficiency in cabbage (Brassica oleracea var. capitata L.). As cabbage lacks the proper mutant for elucidating the mechanism of MYB103 in P deficiency, another member of the crucifer family, Arabidopsis thaliana was chosen for further study. The transcript of its homologue AtMYB103 was also elevated in response to P deficiency in A. thaliana, while disruption of AtMYB103 (myb103) exhibited increased sensitivity to P deficiency, accompanied with decreased tissue biomass and soluble P concentration. Furthermore, AtMYB103 was involved in the P reutilization from cell wall, as less P was released from the cell wall in myb103 than in wildtype, coinciding with the reduction of ethylene production. Taken together, our results uncover an important role of MYB103 in the P remobilization, presumably through ethylene signaling.

scholarly journals Ref2, a regulatory subunit of the yeast protein phosphatase 1, is a novel component of cation homoeostasis

2010 ◽  
Vol 426 (3) ◽  
pp. 355-364 ◽  
Author(s):  
Jofre Ferrer-Dalmau ◽  
Asier González ◽  
Maria Platara ◽  
Clara Navarrete ◽  
José L. Martínez ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Living Organism ◽  
Calcium Sensitivity ◽  
Growth Conditions ◽  
Protein Phosphatase 1 ◽  
Regulatory Subunit ◽  
Alkaline Ph ◽  
Yeast Protein ◽  
Increased Sensitivity

Maintenance of cation homoeostasis is a key process for any living organism. Specific mutations in Glc7, the essential catalytic subunit of yeast protein phosphatase 1, result in salt and alkaline pH sensitivity, suggesting a role for this protein in cation homoeostasis. We screened a collection of Glc7 regulatory subunit mutants for altered tolerance to diverse cations (sodium, lithium and calcium) and alkaline pH. Among 18 candidates, only deletion of REF2 (RNA end formation 2) yielded increased sensitivity to these conditions, as well as to diverse organic toxic cations. The Ref2F374A mutation, which renders it unable to bind Glc7, did not rescue the salt-related phenotypes of the ref2 strain, suggesting that Ref2 function in cation homoeostasis is mediated by Glc7. The ref2 deletion mutant displays a marked decrease in lithium efflux, which can be explained by the inability of these cells to fully induce the Na+-ATPase ENA1 gene. The effect of lack of Ref2 is additive to that of blockage of the calcineurin pathway and might disrupt multiple mechanisms controlling ENA1 expression. ref2 cells display a striking defect in vacuolar morphogenesis, which probably accounts for the increased calcium levels observed under standard growth conditions and the strong calcium sensitivity of this mutant. Remarkably, the evidence collected indicates that the role of Ref2 in cation homoeostasis may be unrelated to its previously identified function in the formation of mRNA via the APT (for associated with Pta1) complex.

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