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https://www.readbyqxmd.com/read/28340076/cisplatin-induced-renal-inflammation-is-ameliorated-by-cilastatin-nephroprotection
#1
Blanca Humanes, Sonia Camaño, Jose Manuel Lara, Venkatta Sabbisetti, María Ángeles González-Nicolás, Joseph V Bonventre, Alberto Tejedor, Alberto Lázaro
Background.: Cisplatin is a potent chemotherapeutic drug whose nephrotoxic effect is a major complication and a dose-limiting factor for antitumoral therapy. There is much evidence that inflammation contributes to the pathogenesis of cisplatin-induced nephrotoxicity. We found that cilastatin, a renal dehydropeptidase-I inhibitor, has protective effects in vitro and in vivo against cisplatin-induced renal damage by inhibiting apoptosis and oxidation. Here, we investigated the potential use of cilastatin to protect against cisplatin-induced kidney injury and inflammation in rats...
March 11, 2017: Nephrology, Dialysis, Transplantation
https://www.readbyqxmd.com/read/28333068/effects-of-reactive-oxygen-species-on-tubular-transport-along-the-nephron
#2
REVIEW
Agustin Gonzalez-Vicente, Jeffrey L Garvin
Reactive oxygen species (ROS) are oxygen-containing molecules naturally occurring in both inorganic and biological chemical systems. Due to their high reactivity and potentially damaging effects to biomolecules, cells express a battery of enzymes to rapidly metabolize them to innocuous intermediaries. Initially, ROS were considered by biologists as dangerous byproducts of respiration capable of causing oxidative stress, a condition in which overproduction of ROS leads to a reduction in protective molecules and enzymes and consequent damage to lipids, proteins, and DNA...
March 23, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28332117/fructose-metabolism-from-a-functional-perspective-implications-for-athletes
#3
REVIEW
Luc Tappy, Robin Rosset
Substantial amounts of fructose are present in our diet. Unlike glucose, this hexose cannot be metabolized by most cells and has first to be converted into glucose, lactate or fatty acids by enterocytes, hepatocytes and kidney proximal tubule cells, which all express specific fructose-metabolizing enzymes. This particular metabolism may then be detrimental in resting, sedentary subjects; however, this may also present some advantages for athletes. First, since fructose and glucose are absorbed through distinct, saturable gut transporters, co-ingestion of glucose and fructose may increase total carbohydrate absorption and oxidation...
March 22, 2017: Sports Medicine
https://www.readbyqxmd.com/read/28331063/microrna-148b-regulates-megalin-expression-and-is-associated-with-receptor-downregulation-in-mice-with-unilateral-ureteral-obstruction
#4
Lu Wen, Pia K Andersen, Dina Mu Husum, Rikke Norregaard, Zhanzheng Zhao, Zhangsuo Liu, Henrik Birn
Megalin is a multiligand, endocytic receptor important for the normal, proximal tubule reabsorption of filtered proteins, hormones, enzymes, essential nutrients, and nephrotoxins. Megalin dysfunction has been associated with acute as well as chronic kidney diseases. Tubular proteinuria has been observed following unilateral ureteral obstruction (UUO) suggesting megalin dysfunction; however, the pathophysiological mechanism has not been resolved. In order to identify potential regulators of megalin expression, we examined renal microRNAs (miRNAs) expression and observed an upregulation of microRNA-148b (miR-148b) in obstructed mouse kidneys 7 days after UUO which was associated with a significant reduction in proximal tubule megalin expression and accumulation of megalin ligands...
March 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28331061/an-intracellular-matrix-metalloproteinase-2-isoform-induces-tubular-regulated-necrosis-implications-for-acute-kidney-injury
#5
Carla S Ceron, Celine Baligand, Sunil K Joshi, Shaynah Wanga, Patrick M Cowley, Joy P Walker, Sang Heon Song, Rajeev Mahimkar, Anthony J Baker, Robert L Raffai, Zhen J Wang, David H Lovett
Acute kidney injury (AKI) causes severe morbidity, mortality, and chronic kidney disease (CKD). Mortality is particularly marked in the elderly and with pre-existing CKD. Oxidative stress is a common theme in models of AKI induced by ischemia/reperfusion (I/R) injury. We recently characterized an intracellular isoform of matrix metalloproteinase-2 (MMP-2) induced by oxidative stress-mediated activation of an alternate promoter in the first intron of the MMP-2 gene. This generates an N-terminal truncated MMP-2 isoform (NTT-MMP-2) that is intracellular and associated with mitochondria...
March 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28331060/proximal-tubule-glutamine-synthetase-expression-is-necessary-for-the-normal-response-to-dietary-protein-restriction
#6
Hyun-Wook Lee, Gunars Osis, Mary E Handlogten, Jill W Verlander, I David Weiner
Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during changes in dietary protein intake. Dietary protein restriction decreases endogenous acid production and ¬decreases urinary ammonia excretion, a major component of net acid excretion. Glutamine synthetase (GS) catalyzes the reaction of NH4+ and glutamate, which regenerates the essential amino acid glutamine and decreases net ammonia generation...
March 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28331059/adaptive-changes-in-gfr-tubular-morphology-and-transport-in-subtotal-nephrectomized-kidneys-modeling-and-analysis
#7
Anita T Layton, Aurélie Edwards, Volker Vallon
Removal of renal mass stimulates anatomical and functional adaptations in the surviving nephrons, including elevation in single-nephron glomerular filtration rate (SNGFR) and tubular hypertrophy. A goal of this study is to assess the extent to which the concomitant increases in filtered load and tubular transport capacity preserve homeostasis of water and salt. To accomplish that goal, we developed computational models to simulate solute transport and metabolism along nephron populations in a uninephrectomized (UNX) rat and a 5/6-nephrectomized (5/6-NX) rat...
March 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28329736/delay-in-renal-hemodynamic-response-to-a-meat-meal-in-severe-obesity
#8
Pietro Anastasio, Davide Viggiano, Miriam Zacchia, Claudia Altobelli, Giovambattista Capasso, Natale Gaspare De Santo
BACKGROUND/AIMS: Little information is available about the tubular functions and the renal adjustments that take place in obese subjects after a protein meal. How the excess fat may affect renal response to dietary proteins is currently only partially understood. This paper aims to address (i) whether severe obesity, in the absence of other comorbidities, is responsible of kidney dysfunction at either the glomerular or the tubular level and (ii) whether it compromises renal adaptations to a large protein meal...
March 23, 2017: Nephron
https://www.readbyqxmd.com/read/28329012/tracking-the-stochastic-fate-of-cells-of-the-renin-lineage-after-podocyte-depletion-using-multicolor-reporters-and-intravital-imaging
#9
Natalya V Kaverina, Hiroyuki Kadoya, Diana G Eng, Michael E Rusiniak, Maria Luisa S Sequeira-Lopez, R Ariel Gomez, Jeffrey W Pippin, Kenneth W Gross, Janos Peti-Peterdi, Stuart J Shankland
Podocyte depletion plays a major role in focal segmental glomerular sclerosis (FSGS). Because cells of the renin lineage (CoRL) serve as adult podocyte and parietal epithelial cell (PEC) progenitor candidates, we generated Ren1cCre/R26R-ConfettiTG/WT and Ren1dCre/R26R-ConfettiTG/WT mice to determine CoRL clonality during podocyte replacement. Four CoRL reporters (GFP, YFP, RFP, CFP) were restricted to cells in the juxtaglomerular compartment (JGC) at baseline. Following abrupt podocyte depletion in experimental FSGS, all four CoRL reporters were detected in a subset of glomeruli at day 28, where they co-expressed de novo four podocyte proteins (podocin, nephrin, WT-1 and p57) and two glomerular parietal epithelial cell (PEC) proteins (claudin-1, PAX8)...
2017: PloS One
https://www.readbyqxmd.com/read/28328292/il-6-is-involved-in-malignancy-and-doxorubicin-sensitivity-of-renal-carcinoma-cells
#10
Yanqiang Chen, Jianzhen Liu, Pei Lv, Jiangyan Gao, Mingzheng Wang, Yongjun Wang
Various survival factors such as the pleiotropic cytokine interleukin-6 (IL-6), a major mediator of inflammation and activator of signal transducer and activator of transcription 3 (STAT3), serve to block apoptosis in cancer cells. Our present study revealed that the expression of IL-6, while not other IL-2, IL-4, IL-8, or IL-10, was significantly elevated in resistance of renal carcinoma cells (RCC) when compared with human renal proximal tubule epithelial cell line HK-2. The inhibition of IL-6 by siRNA can suppress the proliferation, migration and invasion of RCC cells and increase the doxorubicin (Dox) sensitivity...
March 22, 2017: Cell Adhesion & Migration
https://www.readbyqxmd.com/read/28325783/renal-handling-of-ketones-in-response-to-sodium-glucose-cotransporter-2-inhibition-in-patients-with-type-2-diabetes
#11
Ele Ferrannini, Simona Baldi, Silvia Frascerra, Brenno Astiarraga, Elisabetta Barsotti, Aldo Clerico, Elza Muscelli
OBJECTIVE: Pharmacologically induced glycosuria elicits adaptive responses in glucose homeostasis and hormone release, including decrements in plasma glucose and insulin levels, increments in glucagon release, enhanced lipolysis, and stimulation of ketogenesis, resulting in an increase in ketonemia. We aimed at assessing the renal response to these changes. RESEARCH DESIGN AND METHODS: We measured fasting and postmeal urinary excretion of glucose, β-hydroxybutyrate (β-HB), lactate, and sodium in 66 previously reported patients with type 2 diabetes and preserved renal function (estimated glomerular filtration rate ≥60 mL · min(-1) · 1...
March 21, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28325740/proximal-tubulopathy-prime-mover-and-key-therapeutic-target-in-diabetic-kidney-disease
#12
Richard E Gilbert
The current view of diabetic kidney disease, based on meticulously acquired ultrastructural morphometry and the utility of measuring plasma creatinine and urinary albumin, has been almost entirely focused on the glomerulus. While clearly of great importance, changes in the glomerulus are not the major determinant of renal prognosis in diabetes and may not be the primary event in the development of diabetic kidney disease either. Indeed, advances in biomarker discovery and a greater appreciation of tubulointerstitial histopathology and the role of tubular hypoxia in the pathogenesis of chronic kidney disease have given us pause to reconsider the current "glomerulocentric" paradigm and focus attention on the proximal tubule that by virtue of the high energy requirements and reliance on aerobic metabolism render it particularly susceptible to the derangements of the diabetic state...
April 2017: Diabetes
https://www.readbyqxmd.com/read/28323095/megalin-targeted-enhanced-transfection-efficiency-in-cultured-human-hk-2-renal-tubular-proximal-cells-using-aminoglycoside-carboxyalkyl-polyethylenimine-containing-nanoplexes
#13
Fatemeh Oroojalian, Ali Hossein Rezayan, Wayne Thomas Shier, Khalil Abnous, Mohammad Ramezani
Non-viral vectors are of interest as therapeutic gene delivery agents in gene therapy, because they are simple to prepare, easy to modify and have definable safety profiles compared to viral vectors. The potential of gene therapy in the treatment of renal diseases is limited by a lack of effective kidney-targeted gene delivery systems. Aminoglycoside antibiotics gentamicin and neomycin were connected by amide linkages to carboxyl groups on carboxyalkylated-PEI25 (25kDa PEI) or carboxyalkylated-PEI10 (10kDa PEI)...
March 16, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28321485/initial-autophagic-protection-switches-to-disruption-of-autophagic-flux-by-lysosomal-instability-during-cadmium-stress-accrual-in-renal-nrk-52e-cells
#14
W-K Lee, S Probst, M P Santoyo-Sánchez, W Al-Hamdani, I Diebels, J-K von Sivers, E Kerek, E J Prenner, F Thévenod
The renal proximal tubule (PT) is the major target of cadmium (Cd(2+)) toxicity where Cd(2+) causes stress and apoptosis. Autophagy is induced by cell stress, e.g., endoplasmic reticulum (ER) stress, and may contribute to cell survival or death. The role of autophagy in Cd(2+)-induced nephrotoxicity remains unsettled due to contradictory results and lack of evidence for autophagic machinery damage by Cd(2+). Cd(2+)-induced autophagy in rat kidney PT cell line NRK-52E and its role in cell death was investigated...
March 20, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28321043/immunolocalization-of-novel-corticomedullary-tubule-injury-markers-in-cynomolgus-monkeys-treated-with-amphotericin-b
#15
J Eric McDuffie, Jing Ying Ma, Yunhai Zhang, Frederic S Almy, Xiaoyun Wu, Ke Li, Manisha Sonee, Ryan Meng, Michele Rizzolio, Sandra S Snook
Amphotericin B (AmpB) nephrotoxicity was used to assess the utility of drug‑induced kidney injury (DIKI) biomarkers in an exploratory study in male cynomolgus monkeys. All animals had quantifiable levels of AmpB in plasma on days 1 and 4. There were no clinical signs of AmpB‑induced toxicity in this study. The gold standard method used to confirm AmpB‑induced DIKI was anatomic pathology which revealed microscopic lesions with varying grades of severity. Immunolocalization of alpha‑1 microglobulin (α‑1M), kidney injury molecule 1 (KIM‑1), osteopontin (OPN) and neutrophil gelatinase‑associated lipocalin (NGAL) proteins was evaluated in formalin‑fixed, paraffin‑embedded monkey kidney tissue sections...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28317878/kidney-specific-transposon-mediated-gene-transfer-in-vivo
#16
Lauren E Woodard, Jizhong Cheng, Richard C Welch, Felisha M Williams, Wentian Luo, Leslie S Gewin, Matthew H Wilson
Methods enabling kidney-specific gene transfer in adult mice are needed to develop new therapies for kidney disease. We attempted kidney-specific gene transfer following hydrodynamic tail vein injection using the kidney-specific podocin and gamma-glutamyl transferase promoters, but found expression primarily in the liver. In order to achieve kidney-specific transgene expression, we tested direct hydrodynamic injection of a DNA solution into the renal pelvis and found that luciferase expression was strong in the kidney and absent from extra-renal tissues...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28317867/double-knockout-of-bax-and-bak-from-kidney-proximal-tubules-reduces-unilateral-urethral-obstruction-associated-apoptosis-and-renal-interstitial-fibrosis
#17
Shuqin Mei, Lin Li, Qingqing Wei, Jielu Hao, Yunchao Su, Changlin Mei, Zheng Dong
Interstitial fibrosis, a common pathological feature of chronic kidney diseases, is often associated with apoptosis in renal tissues. To determine the associated apoptotic pathway and its role in renal interstitial fibrosis, we established a mouse model in which Bax and Bak, two critical genes in the intrinsic pathway of apoptosis, were deleted specifically from kidney proximal tubules and used this model to examine renal apoptosis and interstitial fibrosis following unilateral urethral obstruction (UUO). It was shown that double knockout of Bax and Bak from proximal tubules attenuated renal tubular cell apoptosis and suppressed renal interstitial fibrosis in UUO...
March 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28315683/klotho-ameliorates-cyclosporine-a-induced-nephropathy-via-pdlim2-nf-kb-p65-signaling-pathway
#18
Meihua Jin, Pengfei Lv, Guanyu Chen, Peng Wang, Zhongfu Zuo, Lili Ren, Jing Bi, Chul-Woo Yang, Xifan Mei, Donghe Han
Klotho, an antiaging protein, can extend the lifespan and modulate cellular responses to inflammation and oxidative stress which can ameliorate chronic kidney diseases (CKD). To investigate the molecular mechanism of Klotho on inflammation in cyclosporine A (CsA) induced nephropathy, the mice were transfected with adenovirus mediated Klotho gene and treated with cyclosporine A (CsA; 30 mg/kg/day) for 4 weeks. Also, primary human renal proximal tubule epithelial cells (RPTECs) were treated with soluble Klotho protein and LPS...
March 15, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28314577/nanotubes-the-fast-track-to-treatment-of-dent-disease
#19
Thomas E Willnow
Studies in mice have suggested bone marrow transplantation as a strategy to correct the endocytic dysfunction of the proximal tubules in renal Fanconi syndrome, yet the mode of action has remained mysterious. Using a mouse model of Dent disease, Gabriel et al. now show that rescue of the resorptive capacity in the diseased kidney involves cell-to-cell contact between engrafted and host cells via nanotubes, cellular projections that enable transfer of wild-type activity into mutant cells of the proximal tubule...
April 2017: Kidney International
https://www.readbyqxmd.com/read/28302370/the-lipid-5-phoshatase-ship2-controls-renal-brush-border-ultrastructure-and-function-by-regulating-the-activation-of-erm-proteins
#20
Sufyan G Sayyed, François Jouret, Marjorie Vermeersch, David Pérez-Morga, Stéphane Schurmans
The microvillus brush border on the renal proximal tubule epithelium allows the controlled reabsorption of solutes that are filtered through the glomerulus and thus participates in general body homeostasis. Here, using the lipid 5-phosphatase Ship2 global knockout mice, proximal tubule-specific Ship2 knockout mice, and a proximal tubule cell model in which SHIP2 is inactivated, we show that SHIP2 is a negative regulator of microvilli formation, thereby controlling solute reabsorption by the proximal tubule...
March 13, 2017: Kidney International
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