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https://www.readbyqxmd.com/read/27916883/enhanced-autophagy-in-polycystic-kidneys-of-aqp11-null-mice
#1
Yasuko Tanaka, Mayumi Watari, Tatsuya Saito, Yoshiyuki Morishita, Kenichi Ishibashi
Aquaporin-11 (AQP11) is an intracellular water channel expressed at the endoplasmic reticulum (ER) of the proximal tubule. Its gene disruption in mice leads to intracellular vacuole formation at one week and the subsequent development of polycystic kidneys by three weeks. As the damaged proximal tubular cells with intracellular vacuoles form cysts later, we postulated that autophagy may play a role in the cyst formation and examined autophagy activity before and after cyst development in AQP11(-/-) kidneys...
November 30, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27914705/pigment-epithelium-derived-factor-a-noninhibitory-serine-protease-inhibitor-is-renoprotective-by-inhibiting-the-wnt-pathway
#2
Xuemin He, Rui Cheng, Kyoungmin Park, Siribhinya Benyajati, Gennadiy Moiseyev, Chengyi Sun, Lorin E Olson, Yanhui Yang, Bonnie K Eby, Kai Lau, Jian-Xing Ma
Pigment epithelium-derived factor (PEDF) expression is downregulated in the kidneys of diabetic rats, and delivery of PEDF suppressed renal fibrotic factors in these animals. PEDF has multiple functions including anti-angiogenic, anti-inflammatory and antifibrotic activities. Since the mechanism underlying its antifibrotic effect remains unclear, we studied this in several murine models of renal disease. Renal PEDF levels were significantly reduced in genetic models of type 1 and type 2 diabetes (Akita and db/db, respectively), negatively correlating with Wnt signaling activity in the kidneys...
November 30, 2016: Kidney International
https://www.readbyqxmd.com/read/27908582/effect-of-curcumin-on-kidney-histopathological-changes-lipid-peroxidation-and-total-antioxidant-capacity-of-serum-in-sodium-arsenite-treated-mice
#3
Hamid Reza Momeni, Najmeh Eskandari
Sodium arsenite is an environmental pollutant with the ability to generate free radicals and curcumin acts as a potent antioxidant. This study investigates the effect of curcumin on kidney histopathology, lipid peroxidation and antioxidant capacity of serum in the mice treated with sodium arsenite. Adult male mice were divided into four groups: control, sodium arsenite, curcumin and curcumin+sodium arsenite. The treatments were delivered for 5 weeks. After the treatment period, blood samples were collected and the concentrations of malondialdehyde (MDA) and total antioxidant capacity of serum were determined...
November 28, 2016: Experimental and Toxicologic Pathology: Official Journal of the Gesellschaft Für Toxikologische Pathologie
https://www.readbyqxmd.com/read/27906618/expression-of-a-human-npt1-slc17a1-missense-variant-which-increases-urate-export
#4
Masayuki Sakiyama, Hirotaka Matsuo, Shushi Nagamori, Wei Ling, Yusuke Kawamura, Akiyoshi Nakayama, Toshihide Higashino, Toshinori Chiba, Kimiyoshi Ichida, Yoshikatsu Kanai, Nariyoshi Shinomiya
Human sodium-dependent phosphate cotransporter type 1 (NPT1/SLC17A1) is one of the urate transporters in the kidney. Our recent study revealed that a common missense variant, I269T (rs1165196), of NPT1 decreases the risk of renal underexcretion gout. Moreover, we demonstrated that human NPT1 is localized to the apical membrane of the renal proximal tubule, and that I269T is the gain-of-function variant which increases the NPT1-mediated urate export. However, the mechanism by which I269T variant increases the urate export remains to be clarified...
December 2016: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/27906063/characterization-of-a-multiprotein-complex-involved-in-excitation-transcription-coupling-of-skeletal-muscle
#5
Manuel Arias-Calderón, Gonzalo Almarza, Alexis Díaz-Vegas, Ariel Contreras-Ferrat, Denisse Valladares, Mariana Casas, Héctor Toledo, Enrique Jaimovich, Sonja Buvinic
BACKGROUND: Electrical activity regulates the expression of skeletal muscle genes by a process known as "excitation-transcription" (E-T) coupling. We have demonstrated that release of adenosine 5'-triphosphate (ATP) during depolarization activates membrane P2X/P2Y receptors, being the fundamental mediators between electrical stimulation, slow intracellular calcium transients, and gene expression. We propose that this signaling pathway would require the proper coordination between the voltage sensor (dihydropyridine receptor, DHPR), pannexin 1 channels (Panx1, ATP release conduit), nucleotide receptors, and other signaling molecules...
April 11, 2016: Skeletal Muscle
https://www.readbyqxmd.com/read/27903492/angiotensinogen-import-in-isolated-proximal-tubules-evidence-for-mitochondrial-trafficking-and-uptake
#6
Bryan A Wilson, Nildris Cruz-Diaz, Yixin Su, James C Rose, TanYa M Gwathmey, Mark C Chappell
The renal proximal tubules are a key functional component of the kidney and express the angiotensin precursor angiotensinogen; however, it is unclear the extent that tubular angiotensinogen reflects local synthesis or internalization. Therefore, the current study established the extent that angiotensinogen is internalized by proximal tubules and the intracellular distribution. Proximal tubules were isolated from the kidney cortex of male sheep by enzymatic digestion and a discontinuous Percoll gradient. Tubules were incubated with radiolabeled 125I-angiotensinogen for 2 hrs at 37°C in serum/phenol-free DMEM/F12 media...
November 30, 2016: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/27895157/beneficial-effects-of-myo-inositol-oxygenase-deficiency-in-cisplatin-induced-aki
#7
Rajesh K Dutta, Vinay K Kondeti, Isha Sharma, Navdeep S Chandel, Susan E Quaggin, Yashpal S Kanwar
Overexpression of the proximal tubular enzyme myo-inositol oxygenase (MIOX) induces oxidant stress in vitro However, the relevance of MIOX to tubular pathobiology remains enigmatic. To investigate the role of MIOX in cisplatin-induced tubular AKI, we generated conditional MIOX-overexpressing transgenic (MIOX-TG) mice and MIOX-knockout (MIOX(-/-)) mice with tubule-specific MIOX overexpression or knockout, respectively. Compared with cisplatin-treated wild-type (WT) mice, cisplatin-treated MIOX-TG mice had even greater increases in urea, creatinine, and KIM-1 levels and more tubular injury and apoptosis, but these effects were attenuated in cisplatin-treated MIOX(-/-) mice...
November 28, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27895154/kidney-tubular-ablation-of-ocrl-inpp5b-phenocopies-lowe-syndrome-tubulopathy
#8
Kazunori Inoue, Daniel M Balkin, Lijuan Liu, Ramiro Nandez, Yumei Wu, Xuefei Tian, Tong Wang, Robert Nussbaum, Pietro De Camilli, Shuta Ishibe
Lowe syndrome and Dent disease are two conditions that result from mutations of the inositol 5-phosphatase oculocerebrorenal syndrome of Lowe (OCRL) and share the feature of impaired kidney proximal tubule function. Genetic ablation of Ocrl in mice failed to recapitulate the human phenotypes, possibly because of the redundant functions of OCRL and its paralog type 2 inositol polyphosphate-5-phosphatase (INPP5B). Germline knockout of both paralogs in mice results in early embryonic lethality. We report that kidney tubule-specific inactivation of Inpp5b on a global Ocrl-knockout mouse background resulted in low molecular weight proteinuria, phosphaturia, and acidemia...
November 28, 2016: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/27894594/alterations-of-golgi-organization-in-alzheimer-s-disease-a-cause-or-a-consequence
#9
REVIEW
Inmaculada Ayala, Antonino Colanzi
The Golgi apparatus is a central organelle of the secretory pathway involved in the post-translational modification and sorting of lipids and proteins. In mammalian cells, the Golgi apparatus is composed of stacks of cisternae organized in polarized manner, which are interconnected by membrane tubules to constitute the Golgi ribbon, located in the proximity of the centrosome. Besides the processing and transport of cargo, the Golgi complex is actively involved in the regulation of mitotic entry, cytoskeleton organization and dynamics, calcium homeostasis, and apoptosis, representing a signalling platform for the control of several cellular functions, including signalling initiated by receptors located at the plasma membrane...
November 19, 2016: Tissue & Cell
https://www.readbyqxmd.com/read/27889773/evaluation-of-kim-1-and-ngal-as-early-indicators-for-assessment-of-gentamycin-induced-nephrotoxicity-in-vivo-and-in-vitro
#10
Qi-Hui Luo, Meng-Lu Chen, Zheng-Li Chen, Chao Huang, An-Chun Cheng, Jing Fang, Li Tang, Yi Geng
BACKGROUND/AIMS: The aminolycoside Gentamicin is a widely used antibiotic, applied in equine medicine. Despite its clinical use, concerns remain regarding the potential toxic side-effects, such as nephrotoxicity. Early detection of renal damage is critical in preclinical drug development. This study was aimed to determine whether kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL) may be early indicators in the assessment of Gentamycin-induced nephrotoxicity...
November 28, 2016: Kidney & Blood Pressure Research
https://www.readbyqxmd.com/read/27882940/mdm2-prevents-spontaneous-tubular-epithelial-cell-death-and-acute-kidney-injury
#11
Dana Thomasova, Martrez Ebrahim, Kristina Fleckinger, Moying Li, Jakob Molnar, Bastian Popper, Helen Liapis, Ahmed M Kotb, Florian Siegerist, Nicole Endlich, Hans-Joachim Anders
Murine double minute-2 (MDM2) is an E3-ubiquitin ligase and the main negative regulator of tumor suppressor gene p53. MDM2 has also a non-redundant function as a modulator of NF-kB signaling. As such it promotes proliferation and inflammation. MDM2 is highly expressed in the unchallenged tubular epithelial cells and we hypothesized that MDM2 is necessary for their survival and homeostasis. MDM2 knockdown by siRNA or by genetic depletion resulted in demise of tubular cells in vitro. This phenotype was completely rescued by concomitant knockdown of p53, thus suggesting p53 dependency...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27882813/dietary-zinc-modifies-diabetic-induced-renal-pathology-in-rats
#12
Wael M Elsaed, Hazem Abdelhamid Mohamed
This study was conducted to investigate how far dietary zinc (Zn) modifies the histomorphological alterations induced by diabetes in rat kidneys. The animals were divided into negative control group (10 rats). Diabetes was induced in thirty animals by streptozotocin. After confirming diabetes, the animals were divided into three groups (n = 10). Group II served as the positive control group (fed on standard diet), group III was fed on Zn deficient diet, and group IV was fed on Zn supplemented diet. Caspase-3 immune staining was used to estimate the caspase activity...
November 24, 2016: Renal Failure
https://www.readbyqxmd.com/read/27878656/mille-modis-morimur-we-die-in-a-thousand-ways
#13
Gaspar Banfalvi
Dying cells subjected to apoptotic programs are engulfed by neighboring cells or by professional phagocytes, without inflammation or immunological reactions in the tissue where apoptosis takes place. Apoptotic cells release danger-associated project signals to their neighbours, through different molecular patterns, stimulate antigen production and immune responses. Microenvironmental effects with several functional consequences indicate that cell death is a complex process and may take place in several ways...
November 23, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27878608/claudins-in-barrier-and-transport-function-the-kidney
#14
REVIEW
Yongfeng Gong, Jianghui Hou
Claudins are discovered to be key players in renal epithelial physiology. They are involved in developmental, physiological, and pathophysiological differentiation. In the glomerular podocytes, claudin-1 is an important determinant of cell junction fate. In the proximal tubule, claudin-2 plays important roles in paracellular salt reabsorption. In the thick ascending limb, claudin-14, -16, and -19 regulate the paracellular reabsorption of calcium and magnesium. Recessive mutations in claudin-16 or -19 cause an inherited calcium and magnesium losing disease...
November 23, 2016: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/27878313/targeting-renal-glucose-reabsorption-to-treat-hyperglycaemia-the-pleiotropic-effects-of-sglt2-inhibition
#15
REVIEW
Volker Vallon, Scott C Thomson
Healthy kidneys filter ∼160 g/day of glucose (∼30% of daily energy intake) under euglycaemic conditions. To prevent valuable energy from being lost in the urine, the proximal tubule avidly reabsorbs filtered glucose up to a limit of ∼450 g/day. When blood glucose levels increase to the point that the filtered load exceeds this limit, the surplus is excreted in the urine. Thus, the kidney provides a safety valve that can prevent extreme hyperglycaemia as long as glomerular filtration is maintained. Most of the capacity for renal glucose reabsorption is provided by sodium glucose cotransporter (SGLT) 2 in the early proximal tubule...
November 22, 2016: Diabetologia
https://www.readbyqxmd.com/read/27873240/improved-safety-and-efficacy-of-213-bi-dotatate-targeted-alpha-therapy-of-somatostatin-receptor-expressing-neuroendocrine-tumors-in-mice-pre-treated-with-l-lysine
#16
Ho Sze Chan, Mark W Konijnenberg, Tamara Daniels, Monique Nysus, Mehran Makvandi, Erik de Blois, Wouter A Breeman, Robert W Atcher, Marion de Jong, Jeffrey P Norenberg
BACKGROUND: Targeted alpha therapy (TAT) offers advantages over current β-emitting conjugates for peptide receptor radionuclide therapy (PRRT) of neuroendocrine tumors. PRRT with (177)Lu-DOTATATE or (90)Y-DOTATOC has shown dose-limiting nephrotoxicity due to radiopeptide retention in the proximal tubules. Pharmacological protection can reduce renal uptake of radiopeptides, e.g., positively charged amino acids, to saturate in the proximal tubules, thereby enabling higher radioactivity to be safely administered...
December 2016: EJNMMI Research
https://www.readbyqxmd.com/read/27867961/cardio-renal-protection-with-empagliflozin
#17
Richard J MacIsaac, George Jerums, Elif I Ekinci
Cardiovascular (CV) and kidney disease are common and significant complications in people with type 2 diabetes (T2DM). CV disease is the leading cause of death, morbidly and hospitalisations for people with T2DM. Furthermore, diabetic kidney disease is a major risk factor for CV disease and is the main reason why patients need renal replacement therapy. In this perspective, we highlight the results of the recent landmark EMPA-REG OUTCOME trial which has shown that empagliflozin, a member of the sodium-glucose co-transporter 2 (SGLT-2) inhibitor class of glucose lowering medications, reduces death from CV causes, hospitalisation for heart failure and progression to end stage kidney disease in patients with T2DM and established CV disease...
October 2016: Annals of Translational Medicine
https://www.readbyqxmd.com/read/27867811/dramatic-mitigation-of-bone-pain-after-phosphorus-replacement-therapy-in-a-subject-with-fgf23-related-hypophosphatemic-osteomalacia
#18
Fuminori Tatsumi, Megumi Horiya, Akihito Tanabe, Momoyo Nishioka, Yoshiro Fushimi, Junpei Sanada, Yurie Hirata, Shintaro Irie, Tomoe Kinoshita, Shinji Kamei, Masashi Shimoda, Tomoatsu Mune, Kohei Kaku, Hideaki Kaneto
INTRODUCTION: Fibroblast growth factor 23 (FGF23) is secreted from bone and suppresses the absorption of phosphorus in renal proximal tubule and in intestinal tract. Therefore, the increase of serum FGF23 levels leads to hypophosphatemic situations. Tumor-induced osteomalacia is often induced by various tumors, but it is often difficult to identify the localization of tumor, because most of the FGF23-producing tumors are small and could be observed in any part of the body. CASE DESCRIPTION: Here we report a case of elderly female subject with FGF23-related hypophosphatemic osteomalacia who repeatedly experienced severe bone pain and fragility fracture in various parts of the body...
2016: SpringerPlus
https://www.readbyqxmd.com/read/27864828/maternal-na-intake-induces-renal-function-injury-in-rats-prevented-by-a-short-term-angiotensin-converting-enzyme-inhibitor
#19
Natalie E Ribeiro, E V Cabral, Regina S Aires, Leucio D Vieira-Filho, Valdilene S Ribeiro, Daianna R M Gonçalves, Luis P N C Borges, Ismaela M F Melo, Cintia G M Ferreira, Valeria Wanderley-Teixeira, Álvaro A C Teixeira, Anísio F Soares, Ana D O Paixão
The Na(+) -ATPase, a secondary pump in the proximal tubule, is only weakly responsive to angiotensin II in adult offspring exposed perinatally to high Na(+) intake. We have investigated whether the offspring from mothers given 0.3 M NaCl show an ineffective angiotensin II action to increase in blood pressure. It was hypothesized that functional alterations at adult life are associated with the number angiotensin II-positive cells in the developing kidney, with increased oxidative stress in maternal/foetal organs, or with morphometrical changes in placentas...
November 19, 2016: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/27864544/investigative-nonclinical-cardiovascular-safety-and-toxicology-studies-with-bms-986094-an-ns5b-rna-dependent-rna-polymerase-inhibitor
#20
M Gill, K Horn, J Hennan, R White, D Bounous, S Clark, J R Megill, E Janovitz, M Davies, T Sanderson, M Graziano
BMS-986094, a 2'-C-methylguanosine prodrug that was in development for treatment of chronic hepatitis C infection was withdrawn from Phase 2 clinical trials because of unexpected cardiac and renal adverse events. Investigative nonclinical studies were conducted to extend the understanding of these findings using more comprehensive endpoints. BMS-986094 was given orally to female CD-1 mice (25 and 150 mg/kg/d) for 2 weeks (53/group) and to cynomolgus monkeys (15 and 30 mg/kg/d) for up to 6 weeks (2-3/sex/group for cardiovascular safety, and 5/sex/group for toxicology)...
November 17, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
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