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https://www.readbyqxmd.com/read/28229902/impact-of-high-glucose-and-ages-on-cultured-kidney-derived-cells-effects-on-cell-viability-lysosomal-enzymes-and-effectors-of-cell-signaling-pathways
#1
Giovani B Peres, Nestor Schor, Yara M Michelacci
We have previously reported decreased expression and activities of lysosomal cathepsins B and L in diabetic kidney. Relevant morphological changes were observed in proximal tubules, suggesting that these cells are implicated in the early stages of the disease. The aim of the present study was to investigate the mechanisms that lead to these changes. The effects of high glucose (HG) and advanced glycation end products (AGEs) on cell viability, lysosomal enzymes and other effectors of cell signaling of cultured kidney cells were studied...
February 13, 2017: Biochimie
https://www.readbyqxmd.com/read/28216050/vancomycin-induces-reactive-oxygen-species-dependent-apoptosis-via-mitochondrial-cardiolipin-peroxidation-in-renal-tubular-epithelial-cells
#2
Yuya Sakamoto, Takahisa Yano, Yuki Hanada, Aki Takeshita, Fumika Inagaki, Satohiro Masuda, Naoya Matsunaga, Satoru Koyanagi, Shigehiro Ohdo
Vancomycin (VCM) is a first-line antibiotic for serious infections caused by methicillin-resistant Staphylococcus aureus. However, nephrotoxicity is one of the most complaint in VCM therapy. We previously reported that VCM induced apoptosis in a porcine proximal tubular epithelial cell line (LLC-PK1), in which mitochondrial complex I may generate superoxide, leading to cell death. In the present study, VCM caused production of mitochondrial reactive oxygen species and peroxidation of the mitochondrial phospholipid cardiolipin that was reversed by administration of the mitochondrial uncoupler carbonyl cyanide-4-(trifluoromethoxy) phenylhydrazone (FCCP)...
February 17, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28214684/modulatory-effect-of-betanin-on-high-glucose-induced-epithelial-to-mesenchymal-transition-in-renal-proximal-tubular-cells
#3
Brijesh Sutariya, Neetika Taneja, Lohit Badgujar, Madhusudan Saraf
No abstract text is available yet for this article.
February 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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
#4
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...
March 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28188286/hydrogen-sulfide-inhibits-high-glucose-induced-nadph-oxidase-4-expression-and-matrix-increment-by-recruiting-inducible-nitric-oxide-synthase-in-the-kidney-proximal-tubular-epithelial-cells
#5
Hak Joo Lee, Doug Yoon Lee, Meenalakshmi M Mariappan, Denis Feliers, Goutam Ghosh Choudhury, Hanna E Abboud, Yves Gorin, Balakuntalam S Kasinath
High glucose increases NADPH oxidase 4 (NOX4) expression, reactive oxygen species (ROS) generation, and, matrix protein synthesis by inhibiting AMP-activated protein kinase (AMPK) in renal cells. Since hydrogen sulfide (H2S) inhibits high glucose-induced matrix protein increment by activating AMPK in renal cells, we examined if H2S inhibits high glucose induced expression of NOX4 and matrix protein and if H2S nitric oxide (NO) pathways are integrated. High glucose increased NOX4 expression and activity at 24 h in renal proximal tubular epithelial cells that was inhibited by sodium hydrosulfide (NaHS), a source of H2S...
February 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28158902/metformin-attenuates-albumin-induced-alterations-in-renal-tubular-cells-in-vitro
#6
Soumaya Allouch, Shankar Munusamy
Proteinuria (albuminuria) plays a crucial role in the etiology of chronic kidney disease (CKD) via alteration of multiple signaling pathways and cellular process in renal cells. The objectives of this study are to investigate the effects of activation of the energy-sensing molecule AMP-activated kinase (AMPK) in renal cells using metformin on endoplasmic reticulum (ER) stress, AKT, mTOR, epithelial-to-mesenchymal transition (EMT), autophagy and apoptosis that are thought to mediate renal cell injury during proteinuria, and to dissect the AMPK- and non-AMPK mediated effects of metformin using an in vitro model of albumin-induced renal cell injury...
February 3, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28151018/calcium-dobesilate-prevents-diabetic-kidney-disease-by-decreasing-bim-and-inhibiting-apoptosis-of-renal-proximal-tubular-epithelial-cells
#7
Tian Cai, Xiao-Yun Wu, Xiao-Qian Zhang, Hong-Xia Shang, Zhong-Wen Zhang, Jian-Jun Dong, Lin Liao
Apoptosis of renal proximal tubular epithelial cells (PTECs) plays a vital role in the pathogenesis and progression of diabetic kidney disease (DKD). Calcium dobesilate is a vascular protective compound used for treatment of diabetic retinopathy and chronic venous insufficiency. The aim of this study was to determine whether calcium dobesilate can protect PTECs from glucose-induced apoptosis and the potential mechanism of this effect. It is indicated that high glucose promoted abnormal apoptosis of HK2 cells, which was inhibited by treatment of calcium dobesilate, while Bim expression decreased in response to calcium dobesilate in high-glucose-treated HK2 cells...
February 2, 2017: DNA and Cell Biology
https://www.readbyqxmd.com/read/28143656/bone-marrow-transplantation-improves-proximal-tubule-dysfunction-in-a-mouse-model-of-dent-disease
#8
Sarah S Gabriel, Hendrica Belge, Alkaly Gassama, Huguette Debaix, Alessandro Luciani, Thomas Fehr, Olivier Devuyst
Dent disease is a rare X-linked tubulopathy caused by mutations in the endosomal chloride-proton exchanger (ClC-5) resulting in defective receptor-mediated endocytosis and severe proximal tubule dysfunction. Bone marrow transplantation has recently been shown to preserve kidney function in cystinosis, a lysosomal storage disease causing proximal tubule dysfunction. Here we test the effects of bone marrow transplantation in Clcn5(Y/-) mice, a faithful model for Dent disease. Transplantation of wild-type bone marrow in Clcn5(Y/-) mice significantly improved proximal tubule dysfunction, with decreased low-molecular-weight proteinuria, glycosuria, calciuria, and polyuria four months after transplantation, compared to Clcn5(Y/-) mice transplanted with ClC-5 knockout bone marrow...
January 28, 2017: Kidney International
https://www.readbyqxmd.com/read/28126415/phenanthrene-derivatives-from-roots-and-rhizomes-of-asarum-heterotropoides-var-mandshuricum
#9
Yu Jing, Yi-Fan Zhang, Ming-Ying Shang, Jie Yu, Jia-Wei Tang, Guang-Xue Liu, Yao-Li Li, Xiao-Mei Li, Xuan Wang, Shao-Qing Cai
Five new phenanthrene derivatives: 9-ethoxy-7-methoxy-aristololactam IV (1), norcepharadione A N-β-d-glucopyranoside (2), aristololactamoside I (3), aristololactamoside II (4) and aristothiolactoside (5) together with eleven known phenanthrene derivatives (6-16) were isolated from the ethanol extract of the roots and rhizomes of Asarum heterotropoides var. mandshuricum. The aristololactams with substitution of ethoxy at C-9 position (1, 9, and 10) and the sulfur-containing phenanthrene derivative (5) were reported in the genus Asarum for the first time...
March 2017: Fitoterapia
https://www.readbyqxmd.com/read/28123498/allicin-inhibits-tubular-epithelial-myofibroblast-transdifferentiation-under-high-glucose-conditions-in-vitro
#10
Hong Huang, Fenping Zheng, Xuehong Dong, Fang Wu, Tianfeng Wu, Hong Li
Previous studies have suggested that tubular epithelial-mesenchymal transition (EMT) is an important event in renal tubulointerstitial fibrosis, which is a clinical characteristic of diabetic nephropathy. The present study aimed to investigate the effect of allicin, the major biological active component of garlic, on the EMT of a human renal proximal tubular epithelial cell line (HK-2) cultured under high glucose concentrations. HK-2 cells were exposed for 48 h to 5.5 or 25 mmol/l D-glucose, 25 mmol/l D-glucose plus allicin (2...
January 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28123102/the-minipig-is-a-suitable-non-rodent-model-in-the-safety-assessment-of-single-stranded-oligonucleotides
#11
A Braendli-Baiocco, M Festag, K Dumong-Erichsen, R Persson, M J Mihatsch, N Fisker, J Funk, S Mohr, R Constien, C Ploix, K Brady, M Berrera, B Altmann, B Lenz, M Albassam, G Schmitt, T Weiser, F Schuler, T Singer, Y Tessier
Non-human primates (NHPs) are currently considered to be the non-rodent species of choice for the preclinical safety assessment of single-stranded oligonucleotide (SSO) drugs. We evaluated minipigs as a potential alternative to NHPs to test the safety of this class of compounds. Four different phosphorothioated locked nucleic acid (LNA)-based SSOs (three antisense and one anti-miR), all with known safety profiles, were administered to minipigs using similar study designs and read-outs as in earlier NHP studies with the same compounds...
January 25, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
https://www.readbyqxmd.com/read/28116093/inhibition-of-sglt2-alleviates-diabetic-nephropathy-by-suppressing-high-glucose-induced-oxidative-stress-in-type-1-diabetic-mice
#12
Takashi Hatanaka, Daisuke Ogawa, Hiromi Tachibana, Jun Eguchi, Tatsuyuki Inoue, Hiroshi Yamada, Kohji Takei, Hirofumi Makino, Jun Wada
It is unclear whether the improvement in diabetic nephropathy by sodium glucose cotransporter 2 (SGLT2) inhibitors is caused by a direct effect on SGLT2 or by the improvement in hyperglycemia. Here, we investigated the effect of dapagliflozin on early-stage diabetic nephropathy using a mouse model of type 1 diabetes and murine proximal tubular epithelial cells. Eight-week-old Akita mice were treated with dapagliflozin or insulin for 12 weeks. Body weight, urinary albumin excretion, blood pressure, as well as levels of blood glucose and hemoglobin A1c were measured...
August 2016: Pharmacology Research & Perspectives
https://www.readbyqxmd.com/read/28094285/urinary-exosomes-contain-micrornas-capable-of-paracrine-modulation-of-tubular-transporters-in-kidney
#13
Tannia Gracia, Xiaonan Wang, Ya Su, Elizabeth E Norgett, Timothy L Williams, Pablo Moreno, Gos Micklem, Fiona E Karet Frankl
Exosomes derived from all nephron segments are present in human urine, where their functionality is incompletely understood. Most studies have focused on biomarker discovery rather than exosome function. Through sequencing we identified the miRNA repertoire of urinary exosomes from healthy volunteers; 276 mature miRNAs and 345 pre-miRNAs were identified (43%/7% of reads). Among the most abundant were members of the miR-10, miR-30 and let-7 families. Targets for the identified miRNAs were predicted using five different databases; genes encoding membrane transporters and their regulators were enriched, highlighting the possibility that these miRNAs could modulate key renal tubular functions in a paracrine manner...
January 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28062795/silac-based-proteomics-of-primary-human-kidney-cells-reveals-a-novel-link-between-male-sex-hormones-and-impaired-energy-metabolism-in-diabetic-kidney-disease
#14
Sergi Clotet, Maria Jose Soler, Marta Riera, Julio Pascual, Fei Fang, Joyce Zhou, Ihor Batruch, Stella K Vasiliou, Apostolos Dimitromanolakis, Clara Barrios, Eleftherios Diamandis, James Scholey, Ana Konvalinka
Male sex predisposes to many kidney diseases. Considering that androgens exert deleterious effects in a variety of cell types within kidney, we hypothesized that dihydrotestosterone (DHT) would alter the biology of the renal tubular cell by inducing changes in the proteome. We employed stable isotope labeling with amino acids (SILAC) in an indirect spike-in fashion to accurately quantify the proteome in DHT- and 17β-estradiol (EST)-treated human proximal tubular epithelial cells (PTEC). Of the 5043 quantified proteins, 76 were differentially regulated...
January 4, 2017: Molecular & Cellular Proteomics: MCP
https://www.readbyqxmd.com/read/28060335/identification-of-intracellular-signaling-events-induced-in-viable-cells-by-interaction-with-neighboring-cells-undergoing-apoptotic-cell-death
#15
Snezana Vujicic, Lanfei Feng, Angelika Antoni, Joyce Rauch, Jerrold S Levine
Cells dying by apoptosis, also referred to as regulated cell death, acquire multiple new activities that enable them to influence the function of adjacent live cells. Vital activities, such as survival, proliferation, growth, and differentiation, are among the many cellular functions modulated by apoptotic cells. The ability to recognize and respond to apoptotic cells appears to be a universal feature of all cells, regardless of lineage or organ of origination. However, the diversity and complexity of the response to apoptotic cells mandates that great care be taken in dissecting the signaling events and pathways responsible for any particular outcome...
December 27, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28053239/microrna-378-reduces-mesangial-hypertrophy-and-kidney-tubular-fibrosis-via-mapk-signaling
#16
Bo Wang, Kevin Yao, Andrea F Wise, Ricky Lau, Hsin-Hui Shen, Greg H Tesch, Sharon D Ricardo
AIMS: To determine the regulatory role of a novel miRNA, miR-378, in the development of fibrosis through repression of the MAPK1 (ERK2) pathway. METHODS: miR-378 and fibrotic gene expression was examined in streptozotocin (STZ)-induced diabetic mice at 18 weeks or in unilateral ureteral obstruction (UUO) mice at 7 days. miR-378 transfection of proximal tubular epithelial cells, NRK52E, and mesangial cells was assessed with/without endogenous miR-378 knockdown using the locked nucleic acid (LNA) inhibitor...
January 4, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28052987/megalin-blockade-with-cilastatin-suppresses-drug-induced-nephrotoxicity
#17
Yoshihisa Hori, Nobumasa Aoki, Shoji Kuwahara, Michihiro Hosojima, Ryohei Kaseda, Sawako Goto, Tomomichi Iida, Shankhajit De, Hideyuki Kabasawa, Reika Kaneko, Hiroyuki Aoki, Yoshinari Tanabe, Hiroshi Kagamu, Ichiei Narita, Toshiaki Kikuchi, Akihiko Saito
Nephrotoxicity induced by antimicrobial or anticancer drugs is a serious clinical problem. Megalin, an endocytic receptor expressed at the apical membranes of proximal tubules, mediates the nephrotoxicity of aminoglycosides and colistin, key antimicrobials for multidrug-resistant organisms. The mechanisms underlying the nephrotoxicity induced by vancomycin, an antimicrobial for methicillin-resistant Staphylococcus aureus, and cisplatin, an important anticancer drug, are unknown, although the nephrotoxicity of these drugs and gentamicin, an aminoglycoside, is suppressed experimentally with cilastatin...
January 4, 2017: Journal of the American Society of Nephrology: JASN
https://www.readbyqxmd.com/read/28049953/cobalt-chloride-induces-expression-and-function-of-breast-cancer-resistance-protein-bcrp-abcg2-in-human-renal-proximal-tubular-epithelial-cell-line-hk-2
#18
Katsuki Nishihashi, Kei Kawashima, Takami Nomura, Yumiko Urakami-Takebayashi, Makoto Miyazaki, Mikihisa Takano, Junya Nagai
The human breast cancer resistance protein (BCRP/ABCG2), a member of the ATP-binding cassette transporter family, is a drug transporter restricting absorption and enhancing excretion of many compounds including anticancer drugs. The cis-regulatory elements in the BCRP promoter include a hypoxia response element, i.e., the DNA binding site for hypoxia-inducible factor-1 (HIF-1). In this study, we investigated the effect of cobalt chloride, a chemical inducer of HIF-1α, on the expression and function of BCRP in human renal proximal tubular cell line HK-2...
2017: Biological & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28042948/bacmam-delivery-of-a-protective-gene-to-reduce-renal-ischemia-reperfusion-injury
#19
Elisabetta Hitchman, Richard Brian Hitchman, Linda A King
Ischaemia-reperfusion (I/R) injury remains the primary contributor to delayed graft function in kidney transplantation. The beneficial application of manganese superoxide dismutase (sod), delivered by a BacMam vector, against renal I/R injury has not been evaluated previously. Therefore, in this study we overexpressed sod-2 in proximal tubular epithelial (HK-2) cells and porcine kidney organs during simulated renal I/R injury. Incubation of HK-2 cells with antimycin A and 2-deoxyglucose resulted in a significant decrease in intracellular ATP levels; following reperfusion, ATP levels significantly increased overtime in cells overexpressing sod-2...
January 2, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28024839/pink1-parkin-mediated-mitophagy-play-a-protective-role-in-cisplatin-induced-renal-tubular-epithelial-cells-injury
#20
Chuanyan Zhao, Zhuyun Chen, Xueqiang Xu, Xiaofei An, Suyan Duan, Zhimin Huang, Chengning Zhang, Lin Wu, Bo Zhang, Aihua Zhang, Changying Xing, Yanggang Yuan
Cisplatin often causes acute kidney injury (AKI) in the treatment of a wide variety of malignancies. Mitochondrial dysfunction is one of the main reasons for cisplatin nephrotoxicity. Previous study showed that Pink1 and Parkin play central roles in regulating the mitophagy, which is a key protective mechanism by specifically eliminating dysfunctional or damaged mitochondria. However, the mechanisms that modulate mitophagy in cisplatin induced nephrotoxicity remain to be elucidated. The purpose of this study was to investigate the effects of Pink1/Parkin pathway in mitophagy, mitochondrial dysfunction and renal proximal tubular cells injury during cisplatin treatment...
December 23, 2016: Experimental Cell Research
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