scholarly journals A role for sodium-chloride cotransporters in the rapid regulation of ion uptake following acute environmental acidosis: new insights from the zebrafish model

2016 ◽  
Vol 311 (6) ◽  
pp. C931-C941 ◽  
Author(s):  
Raymond W. M. Kwong ◽  
Steve F. Perry
Keyword(s):  
Acid Exposure ◽  
Whole Body ◽  
Cell Type ◽  
Acidic Water ◽  
Zebrafish Model ◽  
Larval Zebrafish ◽  
Water Ph ◽  
Control Water ◽  
Compensatory Regulation

The effects of acute exposure to acidic water on Na+ and Cl− homeostasis, and the mechanisms underlying their compensatory regulation, were investigated in the larval zebrafish Danio rerio. Exposure to acidic water (pH 4.0; control pH 7.6) for 2 h significantly reduced Na+ uptake and whole body Na+ content. Nevertheless, the capacity for Na+ uptake was substantially increased in fish preexposed to acidic water but measured in control water. Based on the accumulation of the Na+-selective dye, Sodium Green, two ionocyte subtypes exhibited intracellular Na+ enrichment after preexposure to acidic water: H+-ATPase rich (HR) cells, which coexpress the Na+/H+ exchanger isoform 3b (NHE3b), and a non-HR cell population. In fish experiencing Na+-Cl− cotransporter (NCC) knockdown, we observed no Sodium Green accumulation in the latter cell type, suggesting the non-HR cells were NCC cells. Elimination of NHE3b-expressing HR cells did not prevent the increased Na+ uptake following acid exposure. On the other hand, the increased Na+ uptake was abolished when the acidic water was enriched with Na+ and Cl−, but not with Na+ only, indicating that the elevated Na+ uptake after acid exposure was associated with the compensatory regulation of Cl−. Further examinations demonstrated that acute acid exposure also reduced whole body Cl− levels and increased the capacity for Cl− uptake. Moreover, knockdown of NCC prevented the increased uptake of both Na+ and Cl− after exposure to acidic water. Together, the results of the present study revealed a novel role of NCC in the compensatory regulation of Na+ and Cl− uptake following acute acidosis.

scholarly journals Cortisol regulates epithelial permeability and sodium losses in zebrafish exposed to acidic water

2013 ◽  
Vol 217 (3) ◽  
pp. 253-264 ◽  
Author(s):  
Raymond W M Kwong ◽  
Steve F Perry
Keyword(s):  
Paracellular Permeability ◽  
Acid Exposure ◽  
Whole Body ◽  
Control Fish ◽  
Epithelial Permeability ◽  
Negative Consequences ◽  
Acidic Water ◽  
Peg 4000 ◽  
Water Ph ◽  
Body Absorption

The effects of cortisol on epithelial permeability and sodium (Na+) handling during acid exposure were investigated in larval zebrafish (Danio rerio). The results demonstrated that the whole-body absorption of the paracellular permeability marker polyethylene glycol-4000 (PEG-4000) decreased with increasing levels of exogenous cortisol. Western blot analysis revealed that the abundance of the epithelial tight junction proteins occludin-a and claudin-b was increased after cortisol treatment. Furthermore, translational gene knockdown of claudin-b using an antisense morpholino oligonucleotide caused an increase in the permeability to PEG-4000, which was mitigated by cortisol treatment, further suggesting a role for cortisol in reducing paracellular permeability. Exposure to acidic water (pH 4.0 vs 7.6) caused an expected increase in the diffusive loss of Na+and a decrease in whole-body Na+levels. These disruptive effects of acute acid exposure on Na+balance were reduced by treatment of larvae with exogenous cortisol. Translational knockdown of the glucocorticoid receptor (GR) abolished the effects of cortisol on epithelial PEG permeability, suggesting that activation of GR was probably the major signaling pathway for reducing epithelial permeability. During acid exposure, the epithelial PEG permeability in the GR morphants was significantly higher than in the control fish. Additionally, GR morphants exhibited a more pronounced diffusive loss of Na+than the control fish during acid exposure. These findings suggest that cortisol may help to minimize the negative consequences of acid exposure on Na+homoeostasis via GR-mediated reductions in epithelial permeability and paracellular Na+loss.

Thyroid Hormone in the Pathogenesis of Congenital Intestinal Dysganglionosis

2020 ◽  
Vol 23 (4) ◽  
pp. 285-295
Author(s):  
Fang Wang ◽  
Ping Jing ◽  
Peiyan Zhan ◽  
Hongyi Zhang
Keyword(s):  
Thyroid Hormone ◽  
Intestinal Motility ◽  
The Body ◽  
Enteric Neurons ◽  
Fluorescent Tracers ◽  
Zebrafish Model ◽  
Larval Zebrafish ◽  
Intestinal Length ◽  
Intestinal Dysganglionosis

Introduction The objective of this study is to investigate the role of thyroid hormone (TH) in the pathogenesis of intestinal dysganglionosis (ID). Methods A zebrafish model of congenital hypothyroidism (CH) was created by exposing the larvae to the 6-propyl-2-thiouracil (PTU). The enteric neurons were labeled with anti-HuC/D antibodies. The number of enteric neurons was counted. The larval intestine was dissociated and stained with anti-p75 and anti-α4 integrin antibodies. Mitosis and apoptosis of the p75+ α4 integrin+ enteric neural crest cells (ENCCs) were studied using flow cytometry. Intestinal motility was studied by analyzing the transit of fluorescent tracers. Results PTU (25 mg/L) significantly reduced TH production at 6- and 9-days post fertilization without changing the body length, body weight, and intestinal length of the larvae. Furthermore, PTU inhibited mitosis of ENCCs and reduced the number of enteric neurons throughout the larval zebrafish intestine. Importantly, PTU inhibited intestinal transit of fluorescent tracers. Finally, thyroxine supplementation restored ENCC mitosis, increased the number of enteric neurons, and recovered intestinal motility in the PTU-treated larvae. Conclusions PTU inhibited TH production, reduced the number of enteric neurons, impaired intestinal motility, and impeded ENCC mitosis in zebrafish, suggesting a possible role of CH in the pathogenesis of ID.

Coupling between gamma irradiation, p53 induction and the apoptotic response depends upon cell type in vivo

1995 ◽  
Vol 108 (5) ◽  
pp. 1843-1848 ◽  
Author(s):  
C.A. Midgley ◽  
B. Owens ◽  
C.V. Briscoe ◽  
D.B. Thomas ◽  
D.P. Lane ◽  
...  
Keyword(s):  
P53 Protein ◽  
Whole Body ◽  
Protein Accumulation ◽  
Cell Type ◽  
Apoptotic Response ◽  
Adult Mice ◽  
Specific Manner ◽  
Massive Apoptosis

The accumulation of p53 protein following whole body irradiation of adult mice was studied using a new polyclonal antibody to mouse p53. While dramatic accumulation of the protein was apparent in splenocytes, thymocytes and osteocytes no p53 protein accumulation was detected in the hepatocytes of the irradiated mouse. Thus, the upstream initiating signals that control the induction of p53 are controlled in a tissue specific manner. While massive apoptosis accompanies p53 induction in thymocytes and splenocytes it is not seen in the osteocytes. Thus the downstream consequences of p53 induction are also tightly controlled. These results have profound significance for an understanding of the role of the p53 tumour suppression pathway in different tissues.

Ammonia excretion via Rhcg1 facilitates Na+ uptake in larval zebrafish, Danio rerio, in acidic water

2011 ◽  
Vol 301 (5) ◽  
pp. R1517-R1528 ◽  
Author(s):  
Yusuke Kumai ◽  
Steve F. Perry
Keyword(s):  
Freshwater Fish ◽  
Ammonia Excretion ◽  
Acidic Water ◽  
Chemical Gradients ◽  
Larval Zebrafish ◽  
Zebrafish Larvae ◽  
Pharmacological Data ◽  
Water Ph ◽  
Rh Proteins ◽  
Na Uptake

The involvement of a Na+/H+ exchanger (NHE) in mediating Na+ uptake by freshwater fish is currently debated. Although supported indirectly by empirical molecular and pharmacological data, theoretically its operation should be constrained thermodynamically, owing to unfavorable chemical gradients. Recently, there has been an increasing focus on ammonia channels (Rh proteins) as potentially contributing to Na+ uptake across the freshwater fish gill. In this study, we tested the hypothesis that Rhcg1, a specific apical isoform of Rh protein, is critically important in facilitating Na+ uptake in zebrafish larvae via its interaction with NHE. Treating larvae (4 days postfertilization) with 5-( N-ethyl- N-isopropyl) amiloride (EIPA), an inhibitor of NHE, caused a significant reduction in Na+ uptake in fish reared in acidic water (pH ∼ 4.0). A role for NHE in Na+ uptake was further confirmed by translational knockdown of NHE3b, an isoform of NHE thought to be responsible for Na+/H+ exchange in zebrafish larvae. Exposing the larvae reared in acidic water to 5 mM external ammonium sulfate or increasing the buffering capacity of the water with 10 mM HEPES caused concurrent reductions in ammonia excretion and Na+ uptake. Furthermore, translational knockdown of Rhcg1 significantly reduced ammonia excretion and Na+ uptake in larvae chronically (4 days) or acutely (24 h) exposed to acidic water. Unlike in sham-injected larvae, EIPA did not affect Na+ uptake in fish experiencing Rhcg1 knockdown. Additionally, exposure of larvae to bafilomycin A1 (an inhibitor of H+-ATPase) significantly reduced Na+ uptake in fish reared in acidic water. These observations suggest the existence of multiple mechanisms of Na+ uptake in larval zebrafish in acidic water: one in which Na+ uptake via NHE3b is linked to ammonia excretion via Rhcg1, and another facilitated by H+-ATPase.

scholarly journals The role of cAMP-mediated intracellular signaling in regulating Na+ uptake in zebrafish larvae

2014 ◽  
Vol 306 (1) ◽  
pp. R51-R60 ◽  
Author(s):  
Yusuke Kumai ◽  
Raymond W. M. Kwong ◽  
Steve F. Perry
Keyword(s):  
Protein Trafficking ◽  
Intracellular Signaling ◽  
Whole Body ◽  
Larval Zebrafish ◽  
Zebrafish Larvae ◽  
Β Adrenergic Receptors ◽  
Camp Levels ◽  
Na Uptake ◽  
Stimulation Of

In the current study, the role of cAMP in stimulating Na+ uptake in larval zebrafish was investigated. Treating larvae at 4 days postfertilization (dpf) with 10 μM forskolin or 1 μM 8-bromo cAMP significantly increased Na+ uptake by three-fold and twofold, respectively. The cAMP-dependent stimulation of Na+ uptake was probably unrelated to protein trafficking via microtubules because pretreatment with 200 μM colchicine or 30 μM nocodazole did not attenuate the magnitude of the response. Na+ uptake was stimulated markedly following acute (2 h) exposure to acidic water. The acid-induced increase in Na+ uptake was accompanied by a twofold elevation in whole body cAMP levels and attenuated by inhibiting PKA with 10 μM H-89. Knockdown of Na+-H+ exchanger 3b (NHE3b) attenuated, but did not abolish, the stimulation of Na+ uptake during forskolin treatment. In glial cell missing 2 morphants, in which the role of NHE3b in Na+ uptake is diminished and the Na+-Cl− cotransporter (NCC) becomes the predominant route of Na+ entry, forskolin treatment continued to increase Na+ uptake. These data suggest that at least NHE3b and NCC are targeted by cAMP in zebrafish larvae. Staining of larvae with fluorescent forskolin and propranolol revealed the presence of transmembrane adenylyl cyclase within multiple subtypes of ionocytes expressing β-adrenergic receptors. Taken together, results of the present study demonstrate that cAMP-mediated intracellular signaling may regulate multiple Na+ transporters and plays an important role in regulating Na+ uptake in zebrafish larvae during acute exposure to an acidic environment.

280-LB: Role of A1 and A3 Adenosine Receptors in Whole Body Glucose Metabolism

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 280-LB ◽  
Author(s):  
SHANU JAIN ◽  
DILIP K. TOSH ◽  
MARC REITMAN ◽  
KENNETH A. JACOBSON
Keyword(s):  
Glucose Metabolism ◽  
Adenosine Receptors ◽  
Whole Body

Determinants of maximal whole-body fat oxidation in elite cross-country skiers: Role of skeletal muscle mitochondria

2018 ◽  
Vol 28 (12) ◽  
pp. 2494-2504 ◽  
Author(s):  
Sune Dandanell ◽  
Anne-Kristine Meinild-Lundby ◽  
Andreas B. Andersen ◽  
Paul F. Lang ◽  
Laura Oberholzer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Fat ◽  
Fat Oxidation ◽  
Whole Body ◽  
Muscle Mitochondria ◽  
Skeletal Muscle Mitochondria ◽  
Cross Country

scholarly journals Monoassociation with bacterial isolates reveals the role of colonization, community complexity and abundance on locomotor behavior in larval zebrafish

2021 ◽  
Vol 3 (1) ◽  
Author(s):  
Chelsea A. Weitekamp ◽  
Allison Kvasnicka ◽  
Scott P. Keely ◽  
Nichole E. Brinkman ◽  
Xia Meng Howey ◽  
...  
Keyword(s):  
Total Concentration ◽  
Bacterial Species ◽  
Locomotor Behavior ◽  
Host Cells ◽  
Individual Species ◽  
Zebrafish Model ◽  
Associated Bacteria ◽  
Larval Zebrafish ◽  
Toxicological Studies ◽  
Community Complexity

Abstract Background Across taxa, animals with depleted intestinal microbiomes show disrupted behavioral phenotypes. Axenic (i.e., microbe-free) mice, zebrafish, and fruit flies exhibit increased locomotor behavior, or hyperactivity. The mechanism through which bacteria interact with host cells to trigger normal neurobehavioral development in larval zebrafish is not well understood. Here, we monoassociated zebrafish with either one of six different zebrafish-associated bacteria, mixtures of these host-associates, or with an environmental bacterial isolate. Results As predicted, the axenic cohort was hyperactive. Monoassociation with three different host-associated bacterial species, as well as with the mixtures, resulted in control-like locomotor behavior. Monoassociation with one host-associate and the environmental isolate resulted in the hyperactive phenotype characteristic of axenic larvae, while monoassociation with two other host-associated bacteria partially blocked this phenotype. Furthermore, we found an inverse relationship between the total concentration of bacteria per larvae and locomotor behavior. Lastly, in the axenic and associated cohorts, but not in the larvae with complex communities, we detected unexpected bacteria, some of which may be present as facultative predators. Conclusions These data support a growing body of evidence that individual species of bacteria can have different effects on host behavior, potentially related to their success at intestinal colonization. Specific to the zebrafish model, our results suggest that differences in the composition of microbes in fish facilities could affect the results of behavioral assays within pharmacological and toxicological studies.

The Role of the Representative: Some Empirical Observations on the Theory of Edmund Burke

1959 ◽  
Vol 53 (3) ◽  
pp. 742-756 ◽  
Author(s):  
Heinz Eulau ◽  
John C. Wahlke ◽  
William Buchanan ◽  
Leroy C. Ferguson
Keyword(s):  
Decision Making ◽  
Political Theory ◽  
Empirical Research ◽  
Body Politic ◽  
Whole Body ◽  
Edmund Burke ◽  
Political Systems ◽  
General Consensus ◽  
History Of

The problem of representation is central to all discussions of the functions of legislatures or the behavior of legislators. For it is commonly taken for granted that, in democratic political systems, legislatures are both legitimate and authoritative decision-making institutions, and that it is their representative character which makes them authoritative and legitimate. Through the process of representation, presumably, legislatures are empowered to act for the whole body politic and are legitimized. And because, by virtue of representation, they participate in legislation, the represented accept legislative decisions as authoritative. But agreement about the meaning of the term “representation” hardly goes beyond a general consensus regarding the context within which it is appropriately used. The history of political theory is studded with definitions of representation, usually embedded in ideological assumptions and postulates which cannot serve the uses of empirical research without conceptual clarification.

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