Expression of salt and urea transporters in rat kidney during cisplatin-induced polyuria

Ecelbarger, Carolyn A.; Sands, Jeff M.; Doran, John; Cacini, William; Kishore, Bellamkonda

doi:10.1046/j.1523-1755.2001.00048.x

Cited by 31 publications

(33 citation statements)

References 39 publications

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“…These pictures are representatives of samples obtained from 4 animals from each experimental group. Bars 40 µm collecting duct (Kim et al 2001;ecelbarger et al 2001). The increased urine output, together with the injured renal tubules, and the following loss of the tubular cells to reabsorb water leading to dehydration, might be some of the reasons that could explain the loss of body weight seen in this treatment (Ali et al 2008).…”

Section: Figmentioning

confidence: 99%

Time course of organic anion transporter 5 (Oat5) urinary excretion in rats treated with cisplatin: a novel urinary biomarker for early detection of drug-induced nephrotoxicity

Bulacio

Torres

2014

Arch Toxicol

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Cisplatin is a widely used citostatic drug employed in the treatment of many solid tumors. Its principal side-effect is nephrotoxicity. The organic anion transporter 5 (Oat5) is exclusively expressed in the kidneys. The aim of this study was to evaluate the time course of Oat5 urinary excretion and changes in conventional biomarkers, such as creatinine and urea plasma levels (Urp and Crp), and protein and glucose urinary levels (Pu and Gluu), between others, and compared them to the onset and progression of histological changes after cisplatin treatment. Male Wistar rats were treated with cisplatin with 5 mg/kg b.w., i.p., and experiments were carried out after 2, 4, 7 and 14 days of treatment. Two days after cisplatin administration, only Oat5 urinary excretion was found markedly modified. On day 4, Urp, Crp, PU and GluU were increased. By the seventh day, a severe impairment in tubular architecture was observed, and from this point and thereon, Oat5 urinary excretion and PU showed a tendency to return to their basal values. Meanwhile, Urp, Crp and GluU tended to return to their basal values by the day 14 of treatment, when kidney morphology showed an important recovery. So Oat5 urinary abundance was elevated 2 days after cisplatin treatment, when no modifications of traditional markers of renal injury were still observed. Therefore, the results showed in this work, in addition to previous data obtained by our group, propose that Oat5 urinary excretion might potentially serve as a noninvasive early biomarker of cisplatin-induced nephrotoxicity.

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Section: Figmentioning

confidence: 99%

Time course of organic anion transporter 5 (Oat5) urinary excretion in rats treated with cisplatin: a novel urinary biomarker for early detection of drug-induced nephrotoxicity

Bulacio

Torres

2014

Arch Toxicol

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“…Tissue samples were prepared and immunoblotted by the methods reported earlier (6,14). Briefly, whole tissue homogenates were prepared by homogenizing tissue samples in homogenizing buffer containing protease inhibitors, and protein concentration was determined by BCA Protein Reagent (Pierce, Rockford, IL) and then solubilized in Laemmli sample buffer at 60°C for 20 min.…”

Section: Protocol IImentioning

confidence: 99%

“…Briefly, whole tissue homogenates were prepared by homogenizing tissue samples in homogenizing buffer containing protease inhibitors, and protein concentration was determined by BCA Protein Reagent (Pierce, Rockford, IL) and then solubilized in Laemmli sample buffer at 60°C for 20 min. A semiquantitative immunoblotting approach was used to assess the alterations in protein levels as described previously (6,14). Equality of protein loading was checked by running loading gels and staining the separated proteins with Coomassie blue (Gel Code Blue, Pierce).…”

Section: Protocol IImentioning

confidence: 99%

P2Y2 receptor mRNA and protein expression is altered in inner medullas of hydrated and dehydrated rats: relevance to AVP-independent regulation of IMCD function

Kishore

Krane

Miller

et al. 2005

American Journal of Physiology-Renal Physiology

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. P2Y2 receptor mRNA and protein expression is altered in inner medullas of hydrated and dehydrated rats: relevance to AVPindependent regulation of IMCD function. Am J Physiol Renal Physiol 288: F1164 -F1172, 2005. First published February 1, 2005 doi:10.1152/ajprenal.00199.2004.-Arginine vasopressin (AVP), acting through a cAMP second messenger system, regulates osmotic water permeability (P f) of the collecting duct. In the collecting duct, the activities of cAMP and phosphonositides (PI) are mutually inhibitory. The P2Y2 receptor (P2Y2-R) is a G protein-coupled extracellular nucleotide receptor associated with PI signaling pathway. Previously, we showed that P2Y2-R is expressed in inner medullary collecting duct (IMCD) of rat, and its agonist (ATP/UTP) activation decreased AVP-induced Pf and resulted in enhanced production of prostaglandin E 2. Hydrated and dehydrated states are associated with alterations in the circulating levels of AVP, expression and/or subcellular distribution of AVP-regulated aquaporin-2 water channel in IMCD and thus P f of IMCD. We hypothesized that altered expression and/or signaling via P2Y2-R may also modulate IMCD function in these conditions. Sprague-Dawley rats were subjected to dehydration by water deprivation (48 h) or hydration (48 or 96 h) by providing sucrose water. Hydration or dehydration resulted in marked alterations in mRNA expression (Northern blot analysis and real-time RT-PCR) and protein abundance (Western blot analysis) of P2Y2-R, with hydrated rats showing significantly higher levels compared with dehydrated rats. Sequential hydration and dehydration experiments also revealed that the regulated expression profiles of P2Y2-R mRNA and protein are discordant. Conversely, the expression of V2-R mRNA remained unaltered during hydration and dehydration. Because virtually all renal cells release ATP in a regulated fashion, the observed alterations in P2Y2-R expression in the inner medulla in hydrated and dehydrated states may constitute a novel mechanism of purinergic modulation of IMCD function. purinergic; V2; cAMP; prostanoids; nucleotides RENAL COLLECTING DUCT IS THE site of regulated water transport, which is under the control of arginine vasopressin (AVP). AVP, acting through its V2 receptor on the collecting duct principal cells, and the associated cAMP second messenger pathway, increases osmotic water permeability (Pf) of collecting duct (25,26). AVP has both short-and long-term effects on the collecting duct water permeability (21, 27). However, AVP is not the only agent that regulates water transport in collecting duct. A variety of autocrine and paracrine agents, such as prostaglandin E 2 (PGE 2 ), and endothelin, through their respective receptors and the accompanying phosphoinositide (PI) signaling pathway, decrease osmotic water permeability of collecting duct even in the presence of AVP (10,20). Thus, in the collecting duct, cAMP and PI systems are mutually opposing signaling pathways (36). Hence, the water permeability of collecting duct at any given ti...

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“…Kidneys were gently decapsulated. Cortex and outer medulla were dissected as described previously (Kishore et al 2000;Ecelbarger et al 2001). Briefly, the sharp dissection of cortex and outer medulla was performed on ice and under a dissection microscope.…”

Section: Animals and Treatmentmentioning

confidence: 99%

Cellular and molecular studies on cisplatin-induced apoptotic cell death in rat kidney

Sheikh-Hamad

Cacini

Buckley

et al. 2004

Archives of Toxicology

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Using morphological and molecular approaches, we characterized cisplatin-induced cell necrosis and apoptosis in rat kidney. Male Sprague-Dawley rats ( n=5 per group) received a single intraperitoneal injection of either cisplatin (5 mg/kg) or saline, and were killed on day 5. Functionally, cisplatin-treated rats developed polyuric acute renal failure. Morphologically, kidneys of cisplatin-treated rats showed overt tubular necrosis associated with apoptosis in the corticomedullary junction. Cell necrosis was segment-specific and was distributed in radial fashion at the corticomedullary junction. The apoptosis was limited to discrete cells in apparently intact tubules in the vicinity of the necrosed tubules. The apoptotic changes were confirmed by TUNEL (TdT-mediated deoxyuridine triphosphate nick-end labeling) and staining for cleaved caspase-3. Analysis of outer medullary tissue for apoptosis-related molecules by RNase protection assay revealed a significant increase in the expression of pro-apoptotic mRNAs (caspases 1, 2, and 8, and Bax) in cisplatin-treated rats. On the other hand, the expression of mRNA for the anti-apoptotic Bcl-2 did not change, resulting in a decrease in relative ratio of Bcl-2/Bax, and thus favoring apoptosis. The above changes were paralleled by a marked increase in caspase-3 precursor, the executioner protease. Furthermore, these pro-apoptotic molecular changes were associated with a 3-fold increase in the activity of JNK1 in the outer medulla, but not in the cortex, of cisplatin-treated rat kidneys, localizing to the site of maximal apoptosis. Upregulation of JNK1 activity in the outer medulla was not accompanied by changes in the activities of ERK or p38 kinase. In conclusion, these data suggest that cisplatin-induced apoptotic cell death in native kidney may be mediated by cooperative activation of the JNK1 pathway and Bax in the outer medulla.

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Expression of salt and urea transporters in rat kidney during cisplatin-induced polyuria

Abstract: Changes in the abundance of outer or inner medullary salt or urea transporters are unlikely to play a role in the CP-induced reduction in medullary hypertonicity. However, qualitative changes in UT proteins may affect their functionality and thus may have a role.

Cited by 31 publications

References 39 publications

Time course of organic anion transporter 5 (Oat5) urinary excretion in rats treated with cisplatin: a novel urinary biomarker for early detection of drug-induced nephrotoxicity

Time course of organic anion transporter 5 (Oat5) urinary excretion in rats treated with cisplatin: a novel urinary biomarker for early detection of drug-induced nephrotoxicity

P2Y2 receptor mRNA and protein expression is altered in inner medullas of hydrated and dehydrated rats: relevance to AVP-independent regulation of IMCD function

Cellular and molecular studies on cisplatin-induced apoptotic cell death in rat kidney

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