scholarly journals Impaired Na+−K+-ATPase signaling in renal proximal tubule contributes to hyperuricemia-induced renal tubular injury

2018 ◽  
Vol 50 (3) ◽  
pp. e452-e452 ◽  
Author(s):  
Jing Xiao ◽  
Xiaoli Zhang ◽  
Chensheng Fu ◽  
Qingmei Yang ◽  
Ying Xie ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Renal Proximal Tubule ◽  
Tubular Injury ◽  
Renal Tubular

scholarly journals Evaluation of Novel Biomarkers of Nephrotoxicity in Two Strains of Rat Treated with Cisplatin

2010 ◽  
Vol 38 (6) ◽  
pp. 943-956 ◽  
Author(s):  
Jean-Charles Gautier ◽  
Björn Riefke ◽  
Jakob Walter ◽  
Petra Kurth ◽  
Lou Mylecraine ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
Collecting Duct ◽  
Kidney Injury ◽  
Renal Proximal Tubule ◽  
Tubular Injury ◽  
Sprague Dawley ◽  
Glutathione S Transferase ◽  
Proximal Tubular ◽  
Novel Biomarkers ◽  
Noninvasive Biomarkers

Cisplatin is an anticancer agent that induces renal proximal tubule lesions in many species. Studies were conducted in Sprague-Dawley and Han-Wistar rats to evaluate the utility of novel preclinical biomarkers of nephrotoxicity for renal lesions caused by this compound. Groups of 10 males of each strain were given a single intraperitoneal injection of 0.3, 1, or 3 mg/kg cisplatin and were sacrificed on days 2, 3, and 5. The novel biomarkers α-glutathione-S-transferase (α-GST) (for proximal tubular injury), μ-glutathione-S-transferase (μ-GST) (for distal tubular injury), clusterin (for general kidney injury), and renal papillary antigen-1 (RPA-1) (for collecting duct injury) were measured in urine by enzyme immunoassay. Histologically, degeneration and necrosis of the S3 segment of the renal proximal tubule were observed on day 2 (Han-Wistar) and days 3 and 5 (both strains) at 1 and 3 mg/kg. Results showed that in both strains of rats, urinary α-GST and clusterin can be detected in urine soon after injury, are more sensitive than BUN and serum creatinine, and therefore are usable as noninvasive biomarkers of proximal tubule injury. Changes in both μ-GST or RPA-1 were considered to represent secondary minor effects of proximal tubular injury on distal segments of the nephron.

Stimulation of renal sulfate secretion by metabolic acidosis requires Na+/H+ exchange induction and carbonic anhydrase

2005 ◽  
Vol 289 (1) ◽  
pp. F208-F216 ◽  
Author(s):  
Ryan M. Pelis ◽  
Susan L. Edwards ◽  
Stan C. Kunigelis ◽  
James B. Claiborne ◽  
J. Larry Renfro
Keyword(s):  
Metabolic Acidosis ◽  
Carbonic Anhydrase ◽  
Proximal Tubule ◽  
Brush Border ◽  
Primary Cultures ◽  
Acute Effect ◽  
Renal Proximal Tubule ◽  
Ussing Chambers ◽  
Renal Tubular ◽  
Nhe Isoforms

The acute effect of metabolic acidosis on SO42− secretion by the marine teleost renal proximal tubule was examined. Metabolic acidosis was mimicked in primary cultures of winter flounder renal proximal tubule epithelium (fPTCs) mounted in Ussing chambers by reducing interstitial pH to 7.1 (normally 7.7). fPTCs with metabolic acidosis secreted SO42− at a net rate that was 40% higher than in paired isohydric controls (pH 7.7 on interstitium). The stimulation was completely blocked by the carbonic anhydrase inhibitor methazolamide (100 μM). Although Na+/H+ exchange (NHE) isoforms 1, 2, and 3 were identified in fPTCs by immunoblotting, administering EIPA (20 μM) to the interstitial and luminal bath solutions had no effect on net SO42− secretion by fPTCs with a normal interstitial pH of 7.7. However, EIPA (20 μM) blocked most of the stimulation caused by acidosis when applied to the lumen but not interstitium, demonstrating that induction of brush-border NHE activity is important. In the intact flounder, serum pH dropped 0.4 pH units (pH 7.7 to 7.3, at 2–3 h) when environmental pH was lowered from 7.8 to ∼4.3. Whereas serum [SO42−] was not altered by acidosis, renal tubular SO42− secretion rate was elevated 200%. Thus metabolic acidosis strongly stimulates renal sulfate excretion most likely by a direct effect on active renal proximal tubule SO42− secretion. This stimulation appears to be dependent on inducible brush-border NHE activity.

scholarly journals The lysosomal V-ATPase B1 subunit in proximal tubule is linked to nephropathic cystinosis

2020 ◽  
Author(s):  
Amer Jamalpoor ◽  
Albertien M van Eerde ◽  
Marc R Lilien ◽  
Charlotte AGH van Gelder ◽  
Esther A Zaal ◽  
...  
Keyword(s):  
Metabolic Acidosis ◽  
Proximal Tubule ◽  
Renal Proximal Tubule ◽  
Nephropathic Cystinosis ◽  
Renal Fanconi Syndrome ◽  
Proximal Tubule Cells ◽  
Pathogenic Variants ◽  
Tubule Cells ◽  
Renal Proximal Tubule Cells ◽  
Renal Tubular

AbstractBackgroundRecently, a 23-month-old girl presented with increased granulocyte cystine levels, metabolic acidosis and symptoms of renal Fanconi syndrome. Cystinosis was suspected and treatment with electrolytes and cysteamine, a cystine depleting agent, was started that appeared effective. However, genetic testing did not detect any variants in CTNS (the gene affected in cystinosis) but instead revealed pathogenic variants in ATP6V1B1. ATP6V1B1 encodes the B1 subunit of the vacuolar H+-ATPase (V-ATPase), that is linked to autosomal recessive distal renal tubular acidosis, a metabolic disorder with an inappropriately alkaline urine and deafness. Here, the unknown link between ATP6V1B1 gene deficiency and proximal tubulopathy as well as a possible link to cystinosis pathophysiology was investigated.MethodsWe used CRISPR/Cas9 technology to selectively knockout the ATP6V1B1 or CTNS gene in human renal proximal tubule cells and compare their proteomic and metabolomic profile with isogenic wild type proximal tubule cells.ResultsATP6V1B1 was expressed along the human distal but also the proximal segments of the nephron. Consistent with the clinical data, loss of ATP6V1B1 in renal proximal tubule cells resulted in increased cystine levels with autophagy activation. Further, omics profiling showed that both ATP6V1B1-/- and CTNS-/- cells are in metabolic acidosis with impaired autophagy and signs of proximal tubular epithelial dysfunction.ConclusionWe identified the lysosomal V-ATPase B1 subunit to play an important role in proximal tubule function, regulating cystine transport and autophagy in human renal proximal tubule cells through its interaction with cystinosin and mTOR-signaling.

scholarly journals ATP induces PAD4 in renal proximal tubule cells via P2X7 receptor activation to exacerbate ischemic AKI

2018 ◽  
Vol 314 (2) ◽  
pp. F293-F305 ◽  
Author(s):  
May Rabadi ◽  
Mihwa Kim ◽  
Hongmei Li ◽  
Sang Jun Han ◽  
Yewoon Choi ◽  
...  
Keyword(s):  
Proximal Tubule ◽  
P2x7 Receptor ◽  
Receptor Activation ◽  
Renal Proximal Tubule ◽  
Proximal Tubule Cells ◽  
Tubule Cells ◽  
Renal Proximal Tubule Cells ◽  
Renal Tubular ◽  
P2x7 Receptor Activation ◽  
Expression And Activity

We previously demonstrated that renal tubular peptidylarginine deiminase-4 (PAD4) is induced after ischemia-reperfusion (IR) injury and this induction of PAD4 exacerbates ischemic acute kidney injury (AKI) by promoting renal tubular inflammation and neutrophil infiltration. However, the mechanisms of renal tubular PAD4 induction after IR remain unknown. Here, we tested the hypothesis that ATP, a proinflammatory danger-associated molecular pattern (DAMP) ligand released from necrotic cells after IR injury, induces renal tubular PAD4 and exacerbates ischemic AKI via P2 purinergic receptor activation. ATP as well as ATPγS (a nonmetabolizable ATP analog) induced PAD4 mRNA, protein, and activity in human and mouse renal proximal tubule cells. Supporting the hypothesis that ATP induces renal tubular PAD4 via P2X7 receptor activation, A804598 (a selective P2X7 receptor antagonist) blocked the ATP-mediated induction of renal tubular PAD4 whereas BzATP (a selective P2X7 receptor agonist) mimicked the effects of ATP by inducing renal tubular PAD4 expression and activity. Moreover, ATP-mediated calcium influx in renal proximal tubule cells was blocked by A804598 and was mimicked by BzATP. P2X7 activation by BzATP also induced PAD4 expression and activity in mouse kidney in vivo. Finally, supporting a critical role for PAD4 in P2X7-mediated exacerbation of renal injury, BzATP exacerbated ischemic AKI in PAD4 wild-type mice but not in PAD4-deficient mice. Taken together, our studies show that ATP induces renal tubular PAD4 via P2X7 receptor activation to exacerbate renal tubular inflammation and injury after IR.

Effect of stevioside on PAH transport by isolated perfused rabbit renal proximal tubule

2000 ◽  
Vol 78 (9) ◽  
pp. 737-744 ◽  
Author(s):  
Promsuk Jutabha ◽  
Chaivat Toskulkao ◽  
Varanuj Chatsudthipong
Keyword(s):  
Proximal Tubule ◽  
Inhibitory Effect ◽  
Renal Proximal Tubule ◽  
Tubular Function ◽  
Transepithelial Transport ◽  
Renal Tubules ◽  
Bathing Medium ◽  
Basolateral Side ◽  
Renal Tubular

Stevioside, a non-caloric sweetening agent, is used as a sugar substitute. An influence of stevioside on renal function has been suggested, but little is known about its effect on tubular function. Therefore, the present study was designed to explore the direct effect of stevioside on transepithelial transport of p-aminohippurate (PAH) in isolated S2 segments of rabbit proximal renal tubules using in vitro microperfusion. Addition of stevioside at a concentration of 0.45 mM to either the tubular lumen, bathing medium, or both at the same time had no effect on transepithelial transport of PAH. Similarly, a concentration of 0.70 mM (maximum solubility in the buffer) when present in the lumen, had no effect on PAH transport. However, this concentration in the bathing medium inhibited PAH transport significantly by about 25-35%. The inhibitory effect of stevioside was gradually abolished after it was removed from the bath. Addition of 0.70 mM stevioside to both lumen and bathing medium at the same time produced no added inhibitory effect. Stevioside at this concentration has no effect on Na+/K+-ATPase activity as well as cell ATP content. These findings suggest that stevioside, at a pharmacological concentration of 0.70 mM, inhibits transepithelial transport of PAH by interfering with the basolateral entry step, the rate-limiting step for transepithelial transport. The lack of effect of stevioside on transepithelial transport of PAH on the luminal side and its reversible inhibitory effect on the basolateral side indicate that stevioside does not permanently change PAH transport and should not harm renal tubular function at normal human intake levels.Key words: stevioside, p-aminohippurate, renal proximal tubule.

The Fine Structure of Rat Renal Microbodies and Cytoplasmic Bodies Following Perfusion Fixation

1973 ◽  
Vol 31 ◽  
pp. 620-621
Author(s):  
J. M. Barrett ◽  
P. M. Heidger
Keyword(s):  
Fine Structure ◽  
Proximal Tubule ◽  
Rat Kidney ◽  
Renal Proximal Tubule ◽  
Convincing Evidence ◽  
Cytoplasmic Bodies ◽  
Rat Renal Proximal Tubule ◽  
Renal Proximal Tubule Cells ◽  
Perfusion Fixation

Microbodies have received extensive morphological and cytochemical investigation since they were first described by Rhodin in 1954. To our knowledge, however, all investigations of microbodies and cytoplasmic bodies of rat renal proximal tubule cells have employed immersion fixation. Tisher, et al. have shown convincing evidence of fine structural alteration of microbodies in rhesus monkey kidney following immersion fixation; these alterations were not encountered when in vivo intravascular perfusion was employed. In view of these studies, and the fact that techniques for perfusion fixation have been established specifically for the rat kidney by Maunsbach, it seemed desirable to employ perfusion fixation to study the fine structure and distribution of microbodies and cytoplasmic bodies within the rat renal proximal tubule.

470-P: SIK2 Protects against Renal Tubular Injury by Inhibiting Endoplasmic Reticulum Stress

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 470-P
Author(s):  
XIAOYU LIAO ◽  
BINGYAO LIU ◽  
HONGTING ZHENG
Keyword(s):  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Tubular Injury ◽  
Renal Tubular
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