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Renal proximal tubule

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https://www.readbyqxmd.com/read/28210973/renal-drug-transporters-and-drug-interactions
#1
REVIEW
Anton Ivanyuk, Françoise Livio, Jérôme Biollaz, Thierry Buclin
Transporters in proximal renal tubules contribute to the disposition of numerous drugs. Furthermore, the molecular mechanisms of tubular secretion have been progressively elucidated during the past decades. Organic anions tend to be secreted by the transport proteins OAT1, OAT3 and OATP4C1 on the basolateral side of tubular cells, and multidrug resistance protein (MRP) 2, MRP4, OATP1A2 and breast cancer resistance protein (BCRP) on the apical side. Organic cations are secreted by organic cation transporter (OCT) 2 on the basolateral side, and multidrug and toxic compound extrusion (MATE) proteins MATE1, MATE2/2-K, P-glycoprotein, organic cation and carnitine transporter (OCTN) 1 and OCTN2 on the apical side...
February 16, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28204833/small-heterodimer-partner-attenuates-hydrogen-peroxide-induced-expression-of-cyclooxygenase-2-and-inducible-nitric-oxide-synthase-by-suppression-of-activator-protein-1-and-nuclear-factor-%C3%AE%C2%BAb-in-renal-proximal-tubule-epithelial-cells
#2
Jung Sun Park, Hoon In Choi, Eun Hui Bae, Seong Kwon Ma, Soo Wan Kim
The orphan nuclear receptor, small heterodimer partner (SHP), plays a negative regulatory role in innate immune responses and is involved in various inflammatory signaling pathways. In the present study, we aimed to ascertain whether SHP is effective in preventing hydrogen peroxide (H2O2)-induced kidney tubular inflammation and explored the molecular mechanisms underlying the protective effects of SHP. Renal ischemia/reperfusion (I/R) injury was induced in mice by clamping both renal pedicles for 30 min...
February 9, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28203358/the-renal-effects-of-sglt2-inhibitors-and-a-mini-review-of-the-literature
#3
REVIEW
Vasileios Andrianesis, Spyridoula Glykofridi, John Doupis
Sodium-glucose linked transporter 2 (SGLT2) inhibitors are a new and promising class of antidiabetic agents which target renal tubular glucose reabsorption. Their action is based on the blockage of SGLT2 sodium-glucose cotransporters that are located at the luminal membrane of tubular cells of the proximal convoluted tubule, inducing glucosuria. It has been proven that they significantly reduce glycated hemoglobin (HbA1c), along with fasting and postprandial plasma glucose in patients with type 2 diabetes mellitus (T2DM)...
December 2016: Therapeutic Advances in Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28196131/altered-renal-sodium-handling-and-risk-of-incident-hypertension-results-of-the-olivetti-heart-study
#4
Lanfranco D'Elia, Francesco P Cappuccio, Roberto Iacone, Ornella Russo, Ferruccio Galletti, Pasquale Strazzullo
Renal tubular sodium (Na) handling plays a key role in blood pressure (BP) regulation. Several cross-sectional studies reported a positive association between higher proximal tubule fractional reabsorption of Na and BP, but no prospective investigation has been reported of this possible association. Hence, the purpose of this study was to estimate the predictive role of renal Na handling on the risk of incident hypertension and the changes in BP occurring in the 8-year follow-up observation of a sample of initially normotensive men (The Olivetti Heart Study)...
2017: PloS One
https://www.readbyqxmd.com/read/28196047/a-time-dependent-model-describes-methotrexate-elimination-and-supports-dynamic-modification-of-mrp2-abcc2-activity
#5
Jean-Baptiste Woillard, Jean Debord, Isabelle Benz-de-Bretagne, Franck Saint-Marcoux, Pascal Turlure, Stéphane Girault, Julie Abraham, Sylvain Choquet, Pierre Marquet, Chantal Barin-Le Guellec
BACKGROUND: MRP2/ABCC2, an efflux transporter expressed at the proximal renal tubule, is rate limiting for urine excretion of coproporphyrin (UCP) isomers I and III, translating in high UCP (I/(I+III)) ratio in MRP2-deficient patients presenting with the Dubin-Johnson Syndrome. MRP2 is also a major contributor to methotrexate (MTX) clearance. As MTX is both a substrate and an inhibitor of MRP2, time course of the concentrations of MTX in blood could induce functional modification of MRP2 over time, which in turn can modify its own elimination rate...
February 11, 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28190920/acute-alloxan-renal-toxicity-in-the-rat-initially-causes-degeneration-of-thick-ascending-limbs-of-henle
#6
Yui Terayama, Yasushi Kodama, Tetsuro Matsuura, Kiyokazu Ozaki
Alloxan (AL) is a material well-known to induce diabetes. Prior to inducing a prolonged diabetic state, AL causes acute tubulointerstitial nephritis. However, the precise primary target site and mechanism of its nephrotoxicity remain unclear. The objective of this study was to evaluate the morphological characteristics relevant to acute renal toxicity following AL administration. Rats were intravenously treated with AL. Eight hours after AL treatment, aquaporin 1-negative and Na/K pump-positive thick ascending limbs of Henle (TAL) were degenerated in the outer medulla...
January 2017: Journal of Toxicologic Pathology
https://www.readbyqxmd.com/read/28188231/diurnal-and-long-term-variation-in-plasma-concentrations-and-renal-clearances-of-circulating-markers-of-kidney-proximal-tubular-secretion
#7
Matthew B Rivara, Leila R Zelnick, Andrew N Hoofnagle, Rick Newitt, Russell P Tracy, Mario Kratz, David S Weigle, Bryan R Kestenbaum
BACKGROUND: The renal proximal tubule is essential for removing organic solutes and exogenous medications from the circulation. We evaluated diurnal, prandial, and long-term biological variation of 4 candidate endogenous markers of proximal tubular secretion. METHODS: We used LC-MS to measure plasma and urine concentrations of hippurate (HA), cinnamoylglycine (CMG), indoxyl sulfate (IS), and p-cresol sulfate (PCS) in 25 healthy adults. We measured plasma concentrations of secreted solutes at 13 time points over a 24-h period, and again after 2 weeks and 14 weeks of follow-up...
February 10, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28180992/comprehensive-functional-analysis-of-rab-gtpases-in-drosophila-nephrocytes
#8
Yulong Fu, Jun-Yi Zhu, Fujian Zhang, Adam Richman, Zhanzheng Zhao, Zhe Han
The Drosophila nephrocyte is a critical component of the fly renal system and bears structural and functional homology to podocytes and proximal tubule cells of the mammalian kidney. Investigations of nephrocyte cell biological processes are fundamental to understanding the insect renal system. Nephrocytes are highly active in endocytosis and vesicle trafficking. Rab GTPases regulate endocytosis and trafficking but specific functions of nephrocyte Rabs remain undefined. We analyzed Rab GTPase expression and function in Drosophila nephrocytes and found that 11 out of 27 Drosophila Rabs were required for normal activity...
February 8, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28177761/temporo-spacial-micoranatomical-distribution-of-the-murine-sodium-dependent-ascorbic-acid-transporters-slc23a1-and-slc23a2-in-the-kidney-throughout-development
#9
Peter Karl Eck, Christopher Corpe, Mark Alan Levine
The two membrane transporters Slc23a1 and Slc23a2 mediate ascorbic acid uptake into cells. We recently determined the key role of Slc23a1 in renal re-absorption of ascorbic acid in a knockout mouse model. However, the renal spatial and temporal expression patterns of murine Slc23a1 and Slc23a2 are not defined. This study utilizes database evidence combined with experimental confirmation via in situ hybridization to define spatial and temporal expression of Slc23a1 in the murine kidney. Slc23a1 is expressed in the early proximal tubule, but not in its precursors during embryonic development, and exclusive proximal tubular expression persists throughout the animal's lifetime...
December 20, 2016: Biochemistry and Cell Biology, Biochimie et Biologie Cellulaire
https://www.readbyqxmd.com/read/28165842/stagnation-of-autophagy-a-novel-mechanism-of-renal-lipotoxicity
#10
Yoshitsugu Takabatake, Takeshi Yamamoto, Yoshitaka Isaka
Excessive fat intake can lead to cellular injury and inflammation (termed lipotoxicity), but studies on lipid metabolism in the kidney have been scarce. We recently identified a novel mechanism of lipotoxicity in the kidney proximal tubules especially focusing on the effect of lipid overload on lysosomal function and autophagic activity. Lipid overload basically stimulates macroautophagy/autophagy for renovation of the plasma and organelle membranes, which plays an essential role in maintaining the integrity of proximal tubules...
February 6, 2017: Autophagy
https://www.readbyqxmd.com/read/28161386/podocyturia-parallels-proximal-tubule-dysfunction-in-type-2-diabetes-mellitus-patients-independently-of-albuminuria-and-renal-function-decline-a-cross-sectional-study
#11
Ligia Petrica, Mihaela Vlad, Adrian Vlad, Gheorghe Gluhovschi, Florica Gadalean, Victor Dumitrascu, Roxana Popescu, Cristina Gluhovschi, Petru Matusz, Silvia Velciov, Flaviu Bob, Sorin Ursoniu, Daliborca Vlad
AIMS: Detection of podocytes in the urine of patients with type 2 diabetes may indicate severe injury to the podocytes. In the course of type 2 diabetes the proximal tubule is involved in urinary albumin processing. We studied the significance of podocyturia in relation with proximal tubule dysfunction in type 2 diabetes. METHODS: A total of 86 patients with type 2 diabetes (34-normoalbuminuria; 30-microalbuminuria; 22-macroalbuminuria) and 28 healthy subjects were enrolled in the study and assessed concerning urinary podocytes, podocyte-associated molecules, and biomarkers of proximal tubule dysfunction...
January 20, 2017: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/28155123/p66shc-mediated-toxicity-of-high-dose-%C3%AE-tocopherol-in-renal-proximal-tubule-cells
#12
Dustin K Reed, Anthony Carter, Mehul Dixit, Istvan Arany
α-Tocopherol (TOC) is a widely used supplement known for its role as an antioxidant. Previously, we have shown that TOC elicits adaptive responses by upregulating the ERK/CREB/HO-1 pathway, which depends on its concentration in cultured renal proximal tubule cells (RPTCs). This suggests that high-dose TOC (hTOC) may elicit adverse effects via inflicting oxidative stress. Since the pro-oxidant p66shc is a major mediator of oxidant injury in various models of renal toxicants, we tested the hypothesis that hTOC elicits renal toxicity through activation of p66shc and consequent oxidative stress...
February 2, 2017: Journal of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28149671/macrophage-tgf-%C3%AE-1-and-the-proapoptotic-extracellular-matrix-protein-bigh3-induce-renal-cell-apoptosis-in-prediabetic-and-diabetic-conditions
#13
Robert J Moritz, Richard G LeBaron, Clyde F Phelix, Rajesha Rupaimoole, Hong Seok Kim, Andrew Tsin, Reto Asmis
Metabolically stressed kidney is in part characterized by infiltrating macrophages and macrophage-derived TGF-β1 that promote the synthesis of various ECM molecules. TGF-β1 strongly enhances the expression of the gene TGFBI that encodes a cell-adhesion class, proapoptotic ECM protein called BIGH3. We hypothesized that in a diabetic environment a relationship between infiltrating macrophages, macrophage-derived TGF-β1, and BIGH3 protein promotes renal cell death. To investigate this hypothesis, we used our mouse model of diabetic complications...
July 2016: International Journal of Clinical Medicine
https://www.readbyqxmd.com/read/28148531/primary-proximal-tubule-hyperreabsorption-and-impaired-tubular-transport-counterregulation-determine-glomerular-hyperfiltration-in-diabetes-a-modeling-analysis
#14
Karen Melissa Hallow, Yeshitila Gebremichael, Gabriel Helmlinger, Volker Vallon
Glomerular hypertension and hyperfiltration in early diabetes is associated with development and progression of diabetic kidney disease. The tubular hypothesis of diabetic hyperfiltration proposes that it is initiated by a primary increase in sodium (Na) reabsorption in the proximal tubule (PT) and the resulting tubuloglomerular feedback (TGF) response and lowering of Bowman space pressure (PBow). Here we utilized a mathematical model of the human kidney to investigate over acute and chronic timescales the mechanisms responsible for the magnitude of the hyperfiltration response...
February 1, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28131833/fluid-shear-stress-stimulates-mate2-k-expression-via-nrf2-pathway-activation
#15
Yasunori Fukuda, Misato Kaishima, Toshiyuki Ohnishi, Kimio Tohyama, Ikumi Chisaki, Yusuke Nakayama, Mari Ogasawara-Shimizu, Yuji Kawamata
Accurate prediction of drug-induced renal toxicity is necessary for development of safer drugs for patients. Cellular assay systems that recapitulate physiologically relevant microenvironments have been proposed for correct estimation of drug responses in the human body. However, establishment of such assay systems for accurate prediction of renal toxicity is challenging because of the lack of readily available in vitro assay systems. In this study, we investigated the cellular response to fluid shear stress, which is a characteristic of the environment in the kidney proximal tubules, using microfluidic devices...
January 25, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28126464/stimulation-of-renal-afferent-fibers-leads-to-activation-of-catecholaminergic-and-non-catecholaminergic-neurons-in-the-medulla-oblongata
#16
REVIEW
Erika E Nishi, Beatriz S Martins, Maycon I O Milanez, Nathalia R Lopes, Jose F de Melo, Roberto B Pontes, Adriana C Girardi, Ruy R Campos, Cássia T Bergamaschi
Presympathetic neurons in the rostral ventrolateral medulla (RVLM) including the adrenergic cell groups play a major role in the modulation of several reflexes required for the control of sympathetic vasomotor tone and blood pressure (BP). Moreover, sympathetic vasomotor drive to the kidneys influence natriuresis and diuresis by inhibiting the cAMP/PKA pathway and redistributing the Na(+)/H(+) exchanger isoform 3 (NHE3) to the body of the microvilli in the proximal tubules. In this study we aimed to evaluate the effects of renal afferents stimulation on (1) the neurochemical phenotype of Fos expressing neurons in the medulla oblongata and (2) the level of abundance and phosphorylation of NHE3 in the renal cortex...
January 19, 2017: Autonomic Neuroscience: Basic & Clinical
https://www.readbyqxmd.com/read/28111348/xenobiotic-transporters-and-kidney-injury
#17
REVIEW
Blessy George, Dahea You, Melanie S Joy, Lauren M Aleksunes
Renal proximal tubules are targets for toxicity due in part to the expression of transporters that mediate the secretion and reabsorption of xenobiotics. Alterations in transporter expression and/or function can enhance the accumulation of toxicants and sensitize the kidneys to injury. This can be observed when xenobiotic uptake by carrier proteins is increased or efflux of toxicants and their metabolites is reduced. Nephrotoxic chemicals include environmental contaminants (halogenated hydrocarbon solvents, the herbicide paraquat, the fungal toxin ochratoxin, and heavy metals) as well as pharmaceuticals (certain beta-lactam antibiotics, antiviral drugs, and chemotherapeutic drugs)...
January 20, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28106131/hif-1%C3%AE-induction-during-reperfusion-avoids-maladaptive-repair-after-renal-ischemia-reperfusion-involving-mir127-3p
#18
Elisa Conde, Sara Giménez-Moyano, Laura Martín-Gómez, Macarena Rodríguez, M Edurne Ramos, Elia Aguado-Fraile, Ignacio Blanco-Sanchez, Ana Saiz, María Laura García-Bermejo
Ischemia/reperfusion (I/R) leads to Acute Kidney Injury. HIF-1α is a key factor during organ response to I/R. We previously demonstrated that HIF-1α is induced during renal reperfusion, after ischemia. Here we investigate the role of HIF-1α and the HIF-1α dependent mechanisms in renal repair after ischemia. By interference of HIF-1α in a rat model of renal I/R, we observed loss of expression and mis-localization of e-cadherin and induction of α-SMA, MMP-13, TGFβ, and collagen I. Moreover, we demonstrate that HIF-1α inhibition promotes renal cell infiltrates by inducing IL-1β, TNF-α, MCP-1 and VCAM-1, through NFkB activity...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28101447/functional-coupling-of-v-atpase-and-clc-5
#19
REVIEW
Nobuhiko Satoh, Masashi Suzuki, Motonobu Nakamura, Atsushi Suzuki, Shoko Horita, George Seki, Kyoji Moriya
Dent's disease is an X-linked renal tubulopathy characterized by low molecular weight proteinuria, hypercalciuria and progressive renal failure. Disease aetiology is associated with mutations in the CLCN5 gene coding for the electrogenic 2Cl(-)/H(+) antiporter chloride channel 5 (CLC-5), which is expressed in the apical endosomes of renal proximal tubules with the vacuolar type H(+)-ATPase (V-ATPase). Initially identified as a member of the CLC family of Cl(-) channels, CLC-5 was presumed to provide Cl(-) shunt into the endosomal lumen to dissipate H(+) accumulation by V-ATPase, thereby facilitating efficient endosomal acidification...
January 6, 2017: World Journal of Nephrology
https://www.readbyqxmd.com/read/28099783/ketosis-and-diabetic-ketoacidosis-in-response-to-sglt2-inhibitors-basic-mechanisms-and-therapeutic-perspectives
#20
REVIEW
Hongyu Qiu, Aleksandra Novikov, Volker Vallon
Inhibitors of the sodium-glucose cotransporter SGLT2 are a new class of anti-hyperglycemic drugs that have been approved for the treatment of type 2 diabetes mellitus (T2DM). These drugs inhibit glucose reabsorption in the proximal tubules of the kidney thereby enhancing glucosuria and lowering blood glucose levels. Additional consequences and benefits include a reduction in body weight, uric acid levels, and blood pressure. Moreover, SGLT2 inhibition can have protective effects on the kidney and cardiovascular system in patients with T2DM and high cardiovascular risk...
January 18, 2017: Diabetes/metabolism Research and Reviews
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