Mechanisms underlying the long-term regulation of NHE3 by parathyroid hormone

2008 ◽  
Vol 294 (5) ◽  
pp. F1232-F1237 ◽  
Author(s):  
Camila Nogueira Alves Bezerra ◽  
Adriana Castello Costa Girardi ◽  
Luciene Regina Carraro-Lacroix ◽  
Nancy Amaral Rebouças
Keyword(s):  
Parathyroid Hormone ◽  
Regulatory Region ◽  
Experimental Models ◽  
Cell Surface Expression ◽  
Epithelial Cell Line ◽  
Mrna Levels ◽  
Apical Surface ◽  
Long Term Effects ◽  
Renal Epithelial Cell

The activity of the Na+/H+ exchanger NHE3 is regulated by a number of factors including parathyroid hormone (PTH). In the current study, we used a renal epithelial cell line, the opossum kidney (OKP) cell, to elucidate the mechanisms underlying the long-term effects of PTH on NHE3 transport activity and expression. We observed that NHE3 activity was reduced 6 h after addition of PTH, and this reduction persisted almost unaltered after 24 h. The decrease in activity was associated with diminished NHE3 cell surface expression at 6, 16, and 24 h after PTH addition, total cellular NHE3 protein at 16 and 24 h, and NHE3 mRNA abundance at 24 h. The lower levels of NHE3 mRNA were associated to a small, but significant, decrease in mRNA stability. Additionally, by analyzing the rat NHE3 gene promoter activity in OKP cells, we verified that the regulatory region spanning the segment −152 to +55 was mildly reduced under the influence of PTH. This effect was completely abolished by the presence of the PKA inhibitor KT 5720. In conclusion, long-term exposure to PTH results in reduction of NHE3 mRNA levels due to a PKA-dependent inhibitory effect on the NHE3 promoter and a small reduction of mRNA half-life, and decrease in the total amount of protein which is preceded by endocytosis of the apical surface NHE3. The decreased NHE3 expression is likely to be responsible for the reduction of sodium, bicarbonate, and fluid reabsorption in the proximal tubule consistently perceived in experimental models of PTH disorders.

scholarly journals Developmental conditions modulate DNA methylation at the glucocorticoid receptor gene with cascading effects on expression and corticosterone levels in zebra finches

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Blanca Jimeno ◽  
Michaela Hau ◽  
Elena Gómez-Díaz ◽  
Simon Verhulst
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Glucocorticoid Receptor ◽  
Early Life ◽  
Receptor Gene ◽  
Regulatory Region ◽  
Long Term Effects ◽  
Glucocorticoid Receptor Gene ◽  
Developmental Conditions

Abstract Developmental conditions can impact the adult phenotype via epigenetic changes that modulate gene expression. In mammals, methylation of the glucocorticoid receptor gene Nr3c1 has been implicated as mediator of long-term effects of developmental conditions, but this evidence is limited to humans and rodents, and few studies have simultaneously tested for associations between DNA methylation, gene expression and phenotype. Adverse environmental conditions during early life (large natal brood size) or adulthood (high foraging costs) exert multiple long-term phenotypic effects in zebra finches, and we here test for effects of these manipulations on DNA methylation and expression of the Nr3c1 gene in blood. Having been reared in a large brood induced higher DNA methylation of the Nr3c1 regulatory region in adulthood, and this effect persisted over years. Nr3c1 expression was negatively correlated with methylation at 2 out of 8 CpG sites, and was lower in hard foraging conditions, despite foraging conditions having no effect on Nr3c1 methylation at our target region. Nr3c1 expression also correlated with glucocorticoid traits: higher expression level was associated with lower plasma baseline corticosterone concentrations and enhanced corticosterone reactivity. Our results suggest that methylation of the Nr3c1 regulatory region can contribute to the mechanisms underlying the emergence of long-term effects of developmental conditions in birds, but in our system current adversity dominated over early life experiences with respect to receptor expression.

Long-term effects of intermittent equine parathyroid hormone fragment (ePTH-1-37) administration on bone metabolism in healthy horses

2011 ◽  
Vol 190 (2) ◽  
pp. e130-e134 ◽  
Author(s):  
Katharina U. Weisrock ◽  
Sarah Winkelsett ◽  
William Martin-Rosset ◽  
Wolf-Georg Forssmann ◽  
Nahid Parvizi ◽  
...  
Keyword(s):  
Parathyroid Hormone ◽  
Bone Metabolism ◽  
Long Term Effects

scholarly journals Lactobacillus acidophilus stimulates the expression of SLC26A3 via a transcriptional mechanism

2010 ◽  
Vol 298 (3) ◽  
pp. G395-G401 ◽  
Author(s):  
Geetu Raheja ◽  
Varsha Singh ◽  
Ke Ma ◽  
Redouane Boumendjel ◽  
Alip Borthakur ◽  
...  
Keyword(s):  
Western Blot ◽  
Lactobacillus Acidophilus ◽  
Promoter Activity ◽  
In Vivo Studies ◽  
Mrna Levels ◽  
Long Term Effects ◽  
Exchange Activity

Clinical efficacy of probiotics in treating various forms of diarrhea has been clearly established. However, mechanisms underlying antidiarrheal effects of probiotics are not completely defined. Diarrhea is caused either by decreased absorption or increased secretion of electrolytes and solutes in the intestine. In this regard, the electroneutral absorption of two major electrolytes, Na+ and Cl−, occurs mainly through the coupled operation of Na+/H+ exchangers and Cl−/OH− exchangers. Previous studies from our laboratory have shown that Lactobacillus acidophilus (LA) acutely stimulated Cl−/OH− exchange activity via an increase in the surface levels of the apical anion exchanger SLC26A3 (DRA). However, whether probiotics influence SLC26A3 expression and promoter activity has not been examined. The present studies were, therefore, undertaken to investigate the long-term effects of LA on SLC26A3 expression and promoter activity. Treatment of Caco-2 cells with LA for 6–24 h resulted in a significant increase in Cl−/OH− exchange activity. DRA mRNA levels were also significantly elevated in response to LA treatment starting as early as 8 h. Additionally, the promoter activity of DRA was increased by more than twofold following 8 h LA treatment of Caco-2 cells. Similar to the in vitro studies, in vivo studies using mice gavaged with LA also showed significantly increased DRA mRNA (∼4-fold) and protein expression in the colonic regions as assessed by Western blot analysis and immunofluorescence. In conclusion, increase in DRA promoter activity and expression may contribute to the upregulation of intestinal electrolyte absorption and might underlie the potential antidiarrheal effects of LA.

scholarly journals Modification of peritoneal dialysis model on rabbits: A pilot study

2008 ◽  
Vol 136 (Suppl. 1) ◽  
pp. 38-43
Author(s):  
Snezana Zunic-Bozinovski ◽  
Biljana Stojimirovic ◽  
Zeljko Lausevic ◽  
Slobodan Krstic ◽  
Jasna Trbojevic-Stankovic ◽  
...  
Keyword(s):  
Peritoneal Dialysis ◽  
Pilot Study ◽  
Recovery Period ◽  
Rabbit Model ◽  
Experimental Period ◽  
Experimental Models ◽  
Peritoneal Membrane ◽  
Long Term Effects ◽  
Peritoneal Tissue

INTRODUCTION. Long-term peritoneal dialysis, a well-established method of depuration in end-stage renal disease patients, is assosiated with morphological and functional alterations of the peritoneal membrane due to the use of bioincompatible dialysis solutions. Studying effects of dialysate on the peritoneal tissue in humans is still a challenge due to ethical and technical limitations. There has been a variety of peritoneal dialysis experimental models but without consensus on the ideal model so far. OBJECTIVE. We aimed to develop a new, modified experimental rabbit model of peritoneal dialysis which would be practical, easy to conduct, relatively inexpensive and convenient to study long-term effects of dialysis solution on the peritoneal membrane. METHOD. This pilot study was performed on five healthy Chinchilla rabbits of both sexes. After i.v. Thiopental injection BP 1G, 0.5 ml/kg body mass, a catheter, especially made from Tro-soluset (Troge Medical GmbH, Hamburg, Germany) infusion system, was surgically tunneled from the animals? neck to the abdomen and inserted to the bottom of the peritoneal cavity. After one week recovery period, peritoneal dialysate instillations were performed for four weeks. During the whole five week experimental period a follow-up diary was kept. RESULTS. All procedures were well tolerated by the animals. The rabbits gained body weight, had normal body temperature and no complications were noted. CONCLUSION. The presented modified peritoneal dialysis model is practical, reproducible, does not require sophisticated technology and is well tolerated by the animals. That is why it is convenient for studying long-term effects of dialysate on the rabbit?s peritoneal membrane.

Evidence for a hyporesponsive limbic-hypothalamic-pituitary-adrenal axis following early-life repetitive hypoglycemia in adult male rats

2011 ◽  
Vol 301 (2) ◽  
pp. R484-R490 ◽  
Author(s):  
Ashton E. Lehmann ◽  
Kathleen Ennis ◽  
Michael K. Georgieff ◽  
Raghavendra Rao ◽  
Phu V. Tran
Keyword(s):  
Rat Model ◽  
Early Life ◽  
Regulatory Protein ◽  
Receptor Expression ◽  
Male Rats ◽  
Mrna Levels ◽  
Long Term Effects ◽  
Hypothalamic Pituitary Adrenal ◽  
Lhpa Axis

The developing limbic-hypothalamic-pituitary-adrenal (LHPA) axis is highly vulnerable to programming by early-life environmental factors, including exposure to synthetic glucocorticoids and nutrient deficiencies. Early-life repetitive hypoglycemia (RHG) is a common complication of insulin therapy for type-1 diabetes that may have long-term consequences in adulthood. Recent observations in a rat model of early RHG suggest persistent changes in LHPA axis function, including changes in relevant hormones and affective behaviors, which support a hyperresponsive LHPA axis. Thus, we hypothesized that early RHG would alter the expression of key genes regulating LHPA axis function in adulthood. The present study employed a rat model of insulin-induced RHG spanning postnatal days (P)24–28, a neurodevelopmental equivalent of early childhood in humans, to assess the long-term effects on mRNA levels for proteins relevant to the LHPA function and the corticosterone responses to ACTH stimulation of dispersed adrenocortical cells in vitro and restraint stress in vivo at adulthood. This early RHG model resulted in a hyporesponsive LHPA axis characterized by impaired corticosterone response, increased hippocampal glucocorticoid and mineralocorticoid receptor (GR and MR), decreased hypothalamic corticotropin-releasing hormone, increased adrenal steroidogenic-acute-regulatory protein and GR, and decreased adrenal MR, melanocortin-type-2 receptor and low-density lipoprotein receptor expression. Our findings highlight a complex environmental-gene interaction between RHG and LHPA axis during development that influences regulation of this axis in adulthood. The findings are consistent with the developmental origins of disease and underscore the influences of early-life events on the programming of a major regulatory system.

scholarly journals Regulation of glycosylation of Lamp-1 in the bovine renal epithelial cell line NBL-1 by changes in the concentration of extracellular phosphate

1994 ◽  
Vol 303 (2) ◽  
pp. 613-618 ◽  
Author(s):  
C R Helps ◽  
J D McGivan
Keyword(s):  
Plasma Membrane ◽  
Core Protein ◽  
Phosphate Transport ◽  
Epithelial Cell Line ◽  
Mrna Levels ◽  
Carbohydrate Structure ◽  
Renal Epithelial Cell ◽  
Physiological Importance ◽  
Renal Epithelial Cell Line ◽  
Beta Galactosidase

We have identified the bovine renal homologue of Lamp-1 (lysosomal-associated membrane glycoprotein 1). It has very similar physical characteristics to other Lamp-1 proteins from a wide variety of tissues and species. Partial sequence analysis has shown it to be 61% identical with human Lamp-1 and about 50% identical with rat and mouse Lamp-1. The extent of glycosylation of bovine Lamp-1 alters in response to changes in the concentration of extracellular phosphate. Bovine renal epithelial cells (NBL-1) grown in normal or phosphate-starved medium contain Lamp-1 of 120 kDa. However, if cells are grown in medium containing 8-10 mM phosphate, they contain Lamp-1 of only 100 kDa. The core protein and mRNA levels have been shown to remain constant under both conditions. Therefore the only conclusion is that the extent of Lamp-1 glycosylation must be changing in response to the extracellular concentration of phosphate. Unlike Carlsson and Fukuda [(1990) J. Biol. Chem. 265, 20488-20495], who showed that the human Lamp-1 protein contained polylactosaminoglycan residues, we have been unable to demonstrate the partial deglycosylation of bovine Lamp-1 by endo-beta-galactosidase. This enzyme removes polylactosaminoglycan groups from glycoproteins, and therefore indicates that the carbohydrate structure of bovine Lamp-1 is probably different from that of other Lamp-1 proteins. At present the physiological importance of bovine renal Lamp-1 and the changes in its extent of glycosylation are unknown. In this paper we postulate that Lamp-1 may be involved in the cycling of plasma-membrane proteins to the lysosome. This is based on the finding that the only other known effect of high extracellular phosphate on NBL-1 cells is to cause a decrease in the Vmax. of plasma-membrane-associated Na(+)-dependent phosphate transport [Helps and McGivan (1991) Eur. J. Biochem. 200, 797-803].

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