Essential role of NHE3 in facilitating formate-dependent NaCl absorption in the proximal tubule

2001 ◽  
Vol 281 (2) ◽  
pp. F288-F292 ◽  
Author(s):  
Tong Wang ◽  
Chao-Ling Yang ◽  
Thecla Abbiati ◽  
Gary E. Shull ◽  
Gerhard Giebisch ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Brush Border Membrane ◽  
Cell Model ◽  
Nacl Transport ◽  
Nacl Absorption ◽  
A Cell ◽  
Complete Dependence ◽  
Stimulation Of

The absorption of NaCl in the proximal tubule is markedly stimulated by formate. This stimulation of NaCl transport is consistent with a cell model involving Cl−-formate exchange in parallel with pH-coupled formate recycling due to nonionic diffusion of formic acid or H+-formate cotransport. The formate recycling process requires H+ secretion. Although Na+-H+ exchanger isoform NHE3 accounts for the largest component of H+ secretion in the proximal tubule, 40–50% of the rates of HCO[Formula: see text] absorption or cellular H+ extrusion persist in NHE3 null mice. The purpose of the present investigation is to use NHE3 null mice to directly test the role of apical membrane NHE3 in mediating NaCl absorption stimulated by formate. We demonstrate that formate stimulates NaCl absorption in the mouse proximal tubule microperfused in vivo, but the component of NaCl absorption stimulated by formate is absent in NHE3 null mice. In contrast, stimulation of NaCl absorption by oxalate is preserved in NHE3 null mice, indicating that oxalate-stimulated NaCl absorption is independent of Na+-H+ exchange. The virtually complete dependence of formate-induced NaCl absorption on NHE3 activity raises the possibility that NHE3 and the formate transporters are functionally coupled in the brush border membrane.

scholarly journals PapRIV, a BV-2 microglial cell activating quorum sensing peptide

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yorick Janssens ◽  
Nathan Debunne ◽  
Anton De Spiegeleer ◽  
Evelien Wynendaele ◽  
Marta Planas ◽  
...  
Keyword(s):  
Quorum Sensing ◽  
Cell Model ◽  
Dependent Manner ◽  
Communication Signals ◽  
Gram Positive Bacteria ◽  
A Cell ◽  
Gastro Intestinal Tract

AbstractQuorum sensing peptides (QSPs) are bacterial peptides produced by Gram-positive bacteria to communicate with their peers in a cell-density dependent manner. These peptides do not only act as interbacterial communication signals, but can also have effects on the host. Compelling evidence demonstrates the presence of a gut-brain axis and more specifically, the role of the gut microbiota in microglial functioning. The aim of this study is to investigate microglial activating properties of a selected QSP (PapRIV) which is produced by Bacillus cereus species. PapRIV showed in vitro activating properties of BV-2 microglia cells and was able to cross the in vitro Caco-2 cell model and reach the brain. In vivo peptide presence was also demonstrated in mouse plasma. The peptide caused induction of IL-6, TNFα and ROS expression and increased the fraction of ameboid BV-2 microglia cells in an NF-κB dependent manner. Different metabolites were identified in serum, of which the main metabolite still remained active. PapRIV is thus able to cross the gastro-intestinal tract and the blood–brain barrier and shows in vitro activating properties in BV-2 microglia cells, hereby indicating a potential role of this quorum sensing peptide in gut-brain interaction.

scholarly journals Characterization of renal NaCl and oxalate transport in Slc26a6−/− mice

2019 ◽  
Vol 316 (1) ◽  
pp. F128-F133 ◽  
Author(s):  
Felix Knauf ◽  
Heino Velazquez ◽  
Victoria Pfann ◽  
Zhirong Jiang ◽  
Peter S. Aronson
Keyword(s):  
Blood Pressure ◽  
Proximal Tubule ◽  
Fractional Excretion ◽  
Wild Type ◽  
Nacl Transport ◽  
Lower Blood ◽  
Urine Oxalate

The apical membrane Cl−/oxalate exchanger SLC26A6 has been demonstrated to play a role in proximal tubule NaCl transport based on studies in microperfused tubules. The present study is directed at characterizing the role of SLC26A6 in NaCl homeostasis in vivo under physiological conditions. Free-flow micropuncture studies revealed that volume and Cl− absorption were similar in surface proximal tubules of wild-type and Slc26a6−/− mice. Moreover, the increments in urine flow rate and sodium excretion following thiazide and furosemide infusion were identical in wild-type and Slc26a6−/− mice, indicating no difference in NaCl delivery out of the proximal tubule. The absence of an effect of deletion of SLC26A6 on NaCl homeostasis was further supported by the absence of lower blood pressure in Slc26a6−/− compared with wild-type mice on normal or low-salt diets. Moreover, raising plasma and urine oxalate by feeding mice a diet enriched in soluble oxalate did not affect mean blood pressure. In contrast to the lack of effect of SLC26A6 deletion on NaCl homeostasis, fractional excretion of oxalate was reduced from 1.6 in wild-type mice to 0.7 in Slc26a6−/− mice. We conclude that, although SLC26A6 is dispensable for renal NaCl homeostasis, it is required for net renal secretion of oxalate.

Stimulation of phosphate transport in the proximal tubule by metabolic substrates

1984 ◽  
Vol 247 (4) ◽  
pp. F582-F587 ◽  
Author(s):  
S. R. Gullans ◽  
P. C. Brazy ◽  
L. J. Mandel ◽  
V. W. Dennis
Keyword(s):  
Proximal Tubule ◽  
Fluid Transport ◽  
Initial Rate ◽  
Tricarboxylic Acid Cycle ◽  
Phosphate Transport ◽  
Glucose Absorption ◽  
Metabolic Substrates ◽  
Tricarboxylic Acid Cycle Intermediates ◽  
Stimulation Of

Studies of phosphate transport in the proximal tubule have recently focused on interactions with cellular metabolism. The present studies demonstrate that two fatty acids, valerate and butyrate, and two tricarboxylic acid cycle intermediates, succinate and malate, stimulate net phosphate transport in the rabbit proximal tubule by 34-117%. Valerate had no effect on the total uptake of inorganic [32P]phosphate into suspensions of proximal tubules but did enhance the initial rate of influx. Net fluid transport was unaffected by these substrates although glucose absorption increased by 10-15% following the addition of either valerate or succinate. Since valerate, butyrate, and succinate are known to stimulate gluconeogenesis and respiration, we evaluated the role of gluconeogenesis in the stimulation of phosphate transport. The addition of 3-mercaptopicolinate (1 mM), an inhibitor of gluconeogenesis, did not alter phosphate transport, nor did it prevent the valerate-induced stimulation of phosphate transport. We conclude that valerate, butyrate, succinate, and malate enhance phosphate transport by the proximal convoluted tubule. This action appears to be unrelated to effects on gluconeogenesis and may be related to close links between phosphate transport and oxidative metabolism.

scholarly journals The effect of strontium ranelate on titanium particle-induced periprosthetic osteolysis regulated by WNT/β-catenin signaling in vivo and in vitro

2021 ◽  
Vol 41 (1) ◽  
Author(s):  
Bolun Wang ◽  
Haohui Guo ◽  
Tianxiang Geng ◽  
Kening Sun ◽  
Liang Zhang ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Aseptic Loosening ◽  
Cell Line ◽  
Conditioned Medium ◽  
Strontium Ranelate ◽  
Cell Model ◽  
Periprosthetic Osteolysis ◽  
A Cell

Abstract Aseptic loosening following periprosthetic osteolysis is the primary complication that limits the lifetime of total joint arthroplasty (TJA). The wear particles trigger a chronic inflammation response in the periprosthetic tissue and turn over the bone balance to bone resorption. The present study aimed to investigate the possible effect and mechanism of strontium ranelate (SR), a clinically safe drug for osteoporosis, on particle-induced periprosthetic osteolysis. Thirty-six female C57BL/6j mice underwent tibial Ti-nail implantation to establish an animal model of aseptic loosening. After 12 weeks, micro-CT results showed that strontium ranelate could inhibit periprosthetic bone resorption. In vitro, Ti particles were used to stimulate RAW264.7 cell line to collect conditioned medium, and co-culture MC3T3-E1 cell line with conditioned medium to establish a cell model of aseptic loosening. The results of alkaline phosphatase (ALP) detection, immunofluorescence, and flow cytometry demonstrated that strontium ranelate could regulate the expression of OPG/RANKL, promote differentiation and mineralization, and inhibit apoptosis in osteoblasts. Moreover, we revealed that SR’s exerted its therapeutic effect by down-regulating sclerostin, thereby activating the Wnt/β-catenin signal pathway. Therefore, this research suggests that strontium ranelate could be a potential drug for the prevention and treatment of particle-induced aseptic loosening post-TJA.

scholarly journals Expression and Role of Parathyroid Hormone-Related Protein in Human Renal Proximal Tubule Cells during Recovery from ATP Depletion

1999 ◽  
Vol 10 (2) ◽  
pp. 238-244
Author(s):  
ADOLFO GARCÍA-OCAÑA ◽  
SUSAN C. GALBRAITH ◽  
SCOTT K. VAN WHY ◽  
KAI YANG ◽  
LINA GOLOVYAN ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Recovery Period ◽  
Ischemic Injury ◽  
Atp Depletion ◽  
Proximal Tubule Cell ◽  
Pthrp Expression ◽  
Human Proximal Tubule Cell

Abstract. Parathyroid hormone (PTH)-related protein (PTHrP) is widely expressed in normal fetal and adult tissues and regulates growth and differentiation in a number of organ systems. Although various renal cell types produce PTHrP, and PTHrP expression in rat proximal renal tubules is upregulated in response to ischemic injury in vivo, the role of PTHrP in the kidney is unknown. To study the effects of injury on PTHrP expression and its consequences in more detail, the immortalized human proximal tubule cell line HK-2 was used in an in vitro model of ATP depletion to mimic in vivo renal ischemic injury. These cells secrete PTHrP into conditioned medium and express the type I PTH/PTHrP receptor. Treatment of confluent HK-2 cells for 2 h with substrate-free, glucose-free medium containing the mitochondrial inhibitor antimycin A (1 μM) resulted in 75% depletion of cellular ATP. After an additional 2 h in glucose-containing medium, cellular ATP levels recovered to approximately 75% of baseline levels. PTHrP mRNA levels, as measured in RNase protection assays, peaked at 2 h into the recovery period (at four times baseline expression). The increase in PTHrP mRNA expression was correlated with an increase in PTHrP protein content in HK-2 cells at 2 to 6 h into the recovery period. Heat shock protein-70 mRNA expression was not detectable under baseline conditions but likewise peaked at 2 h into the recovery period. Treatment of HK-2 cells during the recovery period after injury with an anti-PTHrP(1-36) antibody (at a dilution of 1:250) resulted in significant reductions in cell number and uptake of [3H]thymidine, compared with nonimmune serum at the same titer. Similar results were observed in uninjured HK-2 cells. It is concluded that this in vitro model of ATP depletion in a human proximal tubule cell line reproduces the pattern of gene expression previously observed in vivo in rat kidney after ischemic injury and that PTHrP plays a mitogenic role in the proliferative response after energy depletion.

The recombinant lectin-like domain of thrombomodulin inhibits angiogenesis through interaction with Lewis Y antigen

Blood ◽  
2012 ◽  
Vol 119 (5) ◽  
pp. 1302-1313 ◽  
Author(s):  
Cheng-Hsiang Kuo ◽  
Po-Ku Chen ◽  
Bi-Ing Chang ◽  
Meng-Chen Sung ◽  
Chung-Sheng Shi ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Egf Receptor ◽  
Tube Formation ◽  
Endothelial Tube Formation ◽  
A Cell ◽  
Lewis Y ◽  
Tm Domain

AbstractLewis Y Ag (LeY) is a cell-surface tetrasaccharide that participates in angiogenesis. Recently, we demonstrated that LeY is a specific ligand of the recombinant lectin-like domain of thrombomodulin (TM). However, the biologic function of interaction between LeY and TM in endothelial cells has never been investigated. Therefore, the role of LeY in tube formation and the role of the recombinant lectin-like domain of TM—TM domain 1 (rTMD1)—in antiangiogenesis were investigated. The recombinant TM ectodomain exhibited lower angiogenic activity than did the recombinant TM domains 2 and 3. rTMD1 interacted with soluble LeY and membrane-bound LeY and inhibited soluble LeY-mediated chemotaxis of endothelial cells. LeY was highly expressed on membrane ruffles and protrusions during tube formation on Matrigel. Blockade of LeY with rTMD1 or Ab against LeY inhibited endothelial tube formation in vitro. Epidermal growth factor (EGF) receptor in HUVECs was LeY modified. rTMD1 inhibited EGF receptor signaling, chemotaxis, and tube formation in vitro, and EGF-mediated angiogenesis and tumor angiogenesis in vivo. We concluded that LeY is involved in vascular endothelial tube formation and rTMD1 inhibits angiogenesis via interaction with LeY. Administration of rTMD1 or recombinant adeno-associated virus vector carrying TMD1 could be a promising antiangiogenesis strategy.

Possible role of cyclic GMP in stimulus-secretion coupling by salt gland of the duck

1979 ◽  
Vol 237 (5) ◽  
pp. C200-C204 ◽  
Author(s):  
D. J. Stewart ◽  
J. Sax ◽  
R. Funk ◽  
A. K. Sen
Keyword(s):  
Cyclic Amp ◽  
Guanylate Cyclase ◽  
Cyclic Gmp ◽  
Salt Gland ◽  
Domestic Ducks ◽  
Stimulus Secretion Coupling ◽  
Stimulation Of

Stimulation of salt galnd secretion in domestic ducks in vivo increased the cyclic GMP concentration of the tissue, but had no effect on cyclic AMP levels. Methacholine, which is known to stimulate sodium transport by the glands both in vivo and in vitro, stimulated ouabain-sensitive respiration in salt gland slices. Cyclic GMP stimulated ouabain-sensitive respiration to the same extent as methacholine. Guanylate cyclase stimulators, hydroxylamine and sodium azide, also stimulated ouabain-sensitive respiration. The stimulation of ouabain-sensitive respiration by methacholine was blocked either by atropine or by removal of calcium from the incubation medium. The stimulation of ouabain-sensitive respiration by cyclic GMP still occurred in the absence of calcium. The above observations seem to indicate that cyclic GMP acts as a tertiary link in the process of stimulus-secretion coupling in the tissue.

Increased fluid absorption and cell volume in isolated rabbit proximal straight tubules after in vivo DOCA administration

1981 ◽  
Vol 241 (5) ◽  
pp. F502-F508 ◽  
Author(s):  
M. A. Knepper ◽  
M. B. Burg
Keyword(s):  
Proximal Tubule ◽  
Cell Volume ◽  
Fluid Transport ◽  
Sodium Intake ◽  
Plasma Concentrations ◽  
Dietary Sodium ◽  
Fluid Absorption ◽  
Direct Stimulation ◽  
Stimulation Of

To investigate whether mineralocorticoids affect the intrinsic capacity of the proximal tubule to absorb sodium and fluid, rabbits were chronically treated a number of ways to systematically vary plasma concentrations of mineralocorticoid hormones. The rate of fluid absorption and tubule dimensions were measured in superficial S2 segments from these rabbits. Chronic administration of deoxycorticosterone acetate (DOCA) was associated with a 67% increase in fluid absorption and a 29% increase in cell volume per unit tubule length. However, neither adrenalectomy nor low sodium diet significantly affected either fluid absorption or cell volume. Furthermore, marked dietary sodium restriction prevented the response to DOCA. We conclude that the DOCA-induced increases in fluid absorption and cell volume do not result from a direct stimulation of the proximal tubular cells by the steroid but more likely are responses to systemic effects of DOCA administration that are dependent on the level of sodium intake. Thus, we find no evidence for a direct mineralocorticoid stimulation of sodium and fluid transport by the S2 portion of the proximal tubule.

scholarly journals Anti-Inflammatory Properties of Mineral-Balanced Deep Sea Water in In-Vitro and In-Vivo Models of Inflamed Intestinal Epithelium

2020 ◽  
Vol 10 (15) ◽  
pp. 5183
Author(s):  
Jain Nam ◽  
Kyeong Jin Kim ◽  
Geonhee Park ◽  
Byeong Goo Kim ◽  
Gwi-Hwa Jeong ◽  
...  
Keyword(s):  
Deep Sea ◽  
Sea Water ◽  
Cell Model ◽  
Mineral Waters ◽  
In Vivo Models ◽  
Deep Sea Water ◽  
High Calcium ◽  
A Cell

This study aimed to determine the effect of deep-sea water (DSW)-derived mineral waters on intestinal health, using a cell model and a dextran sulfate sodium (DSS)-induced enteritis mouse model. DSW was desalted and minerals were added to generate mineral waters that were classified as trace mineral (TM), high magnesium (HM), high magnesium low salt (HMLS), and high magnesium high calcium (HMHC), using a tabletop electrodialysis device. Caco-2 cells cocultured with Raw264.7 cells were either pre-treated or not with the four water groups, and inflammation was induced by treatment with lipopolysaccharide (LPS). Compared to LPS-treated Caco-2 cells, HMLS-cotreated cells maintained high transepithelial electrical resistance, similar to control cells. FITC-dextran permeability was lower in HMLS-treated than in other cells. In vivo, in comparison to DSS-treated mice, colon shortening was inhibited, and disease activity and colon injury were suppressed in HMLS-cotreated mice. RNA-seq of colonic tissues revealed that inflammatory gene expression was similar among the control and HMLS mice, and DSS-induced expression of inflammation-related genes such as TNF-α and NOS2 and inflammatory chemokine genes was suppressed. Our findings suggest that DSW-derived mineral water intake can help reduce colitis symptoms, and the effects may be partially regulated by magnesium and other minerals.

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