scholarly journals Altered Renal Expression of Relevant Clinical Drug Transporters in Different Models of Acute Uremia in Rats. Role of Urea Levels

2015 ◽  
Vol 36 (3) ◽  
pp. 907-916 ◽  
Author(s):  
Anabel Brandoni ◽  
Adriana M. Torres
Keyword(s):  
Protein Expression ◽  
Plasma Membranes ◽  
Organic Anion ◽  
The Body ◽  
Dependent Manner ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Renal Expression

Background/Aims: Organic anion transporter 1 (Oat1) and 3 (Oat3) are organic anion transporters that play critical roles in the body disposition of numerous clinically important drugs. We investigated the effects of acute uremia on the renal expression of Oat1 and Oat3 in three in vivo experimental models of acute kidney injury (AKI): induced by ischemia, by ureteral obstruction and by the administration of HgCl2. We also evaluated the influence of urea in the expression of these transporters in proximal tubular cells suspensions. Methods: Membranes were isolated from kidneys of each experimental group and from cell suspensions incubated with different urea concentrations. Oat1 and Oat3 expressions were performed by immunoblotting. Results: A good correlation between uremia and the renal protein expression of Oat1 and Oat3 was observed in vivo. Moreover, the incubation of isolated proximal tubular cells with different concentrations of urea decreases protein expression of Oat1 and Oat3 in plasma membranes in a dose-dependent manner. Conclusion: The more severe the renal failure, the more important is the decrease in protein expression of the transporters in renal membranes where they are functional. The in vitro study demonstrates that urea accounts, at least in part, for the decreased expression of Oat1 and Oat3 in proximal tubule plasma membranes.

Membrane Nanoparticles Derived from ACE2-rich Cells Block SARS-CoV-2 Infection

2020 ◽  
Author(s):  
Cheng Wang ◽  
Shaobo Wang ◽  
Yin Chen ◽  
Jianqi Zhao ◽  
Songling Han ◽  
...  
Keyword(s):  
Viral Entry ◽  
Inhibitory Concentration ◽  
Cell Metabolism ◽  
Host Cells ◽  
Dependent Manner ◽  
Human Embryonic Kidney ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Dose Dependent

ABSTRACTThe ongoing COVID-19 epidemic worldwide necessitates the development of novel effective agents against SARS-CoV-2. ACE2 is the main receptor of SARS-CoV-2 S1 protein and mediates viral entry into host cells. Herein, the membrane nanoparticles prepared from ACE2-rich cells are discovered with potent capacity to block SARS-CoV-2 infection. The membrane of human embryonic kidney-239T cell highly expressing ACE2 is screened to prepare nanoparticles. The nanomaterial termed HEK-293T-hACE2 NPs contains 265.1 ng mg−1 of ACE2 on the surface and acts as a bait to trap SARS-CoV-2 S1 in a dose-dependent manner, resulting in reduced recruitment of the viral ligand to host cells. Interestingly, SARS-CoV-2 S1 can translocate to the cytoplasm and affect the cell metabolism, which is also inhibited by HEK-293T-hACE2 NPs. Further studies reveal that HEK-293T-hACE2 NPs can efficiently suppress SARS-CoV-2 S pseudovirions entry into human proximal tubular cells and block viral infection with a low half maximal inhibitory concentration. Additionally, this biocompatible membrane nanomaterial is sufficient to block the adherence of SARS-CoV-2 D614G-S1 mutant to sensitive cells. Our study demonstrates a easy-to-acheive memrbane nano-antagonist for curbing SARS-CoV-2, which enriches the existing antiviral arsenal and provides new possibilities to treat COVID-19. Graphical Table of Contents

ANG II is a mitogen for a murine cell line isolated from medullary thick ascending limb of Henle's loop

1995 ◽  
Vol 268 (5) ◽  
pp. F940-F947 ◽  
Author(s):  
G. Wolf ◽  
F. N. Ziyadeh ◽  
U. Helmchen ◽  
G. Zahner ◽  
R. Schroeder ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Cell Line ◽  
Thick Ascending Limb ◽  
Dependent Manner ◽  
Ang Ii ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Medullary Thick Ascending Limb ◽  
Henle's Loop ◽  
Proximal Tubular

A murine SV40-transformed renal epithelial cell line derived from medullary thick ascending limb of Henle's loop (MTAL) was established and characterized by morphology, antigen expression, and biochemical criteria. These MTAL cells express a single class of high-affinity receptors for angiotensin II (ANG II) and transcripts for the AT1 subtype of ANG II receptors. ANG II, in a dose-dependent manner, induced proliferation of MTAL cells. This observation is in striking contrast to syngeneic proximal tubular cells in which it was previously shown that the peptide induced cellular hypertrophy and slightly inhibited proliferation [G. Wolf and E. G. Neilson. Am. J. Physiol. 259 (Renal Fluid Electrolyte Physiol. 28: F768-F777, 1990]. The AT1-receptor antagonist losartan (10(-6) M), but not an AT2-receptor antagonist, blocked the mitogenic effects of ANG II in MTAL cells. Coincubation of quiescent MTAL cells with ANG II and 5% fetal calf serum further increased proliferation compared with cells grown only in serum. In contrast to proximal tubular cells, ANG II failed to induce transforming growth factor-beta 1 mRNA and protein synthesis in MTAL cells. Our data collectively suggest that ANG II is a mitogen for MTAL cells in vitro. Therefore, epithelial cells derived from different parts of the nephron, even when transformed with SV40 virus and while under cell culture conditions, exhibit a distinct pattern of growth behavior after stimulation with ANG II.

Coincident microvillar actin bundle disruption and perinuclear actin sequestration in anoxic proximal tubule

2000 ◽  
Vol 278 (6) ◽  
pp. F886-F893 ◽  
Author(s):  
Peter White ◽  
R. Brian Doctor ◽  
Rolf H. Dahl ◽  
Jing Chen
Keyword(s):  
Control Level ◽  
Dependent Manner ◽  
Differential Interference Contrast ◽  
Differential Interference Contrast Microscopy ◽  
Proximal Tubular Cells ◽  
Actin Bundle ◽  
Tubular Cells ◽  
Contrast Microscopy ◽  
Proximal Tubular ◽  
Interference Contrast Microscopy

The present studies investigated acute disruption of microvillar actin cytoskeleton and actin association with other cytoskeletal components in ATP-depleted rabbit proximal tubular cells. Video-enhanced differential-interference contrast microscopy and confocal microscopy were used to follow the fate of F-actin during the disruption of microvilli. Within individual cells, all microvilli collapsed simultaneously. Microvillar actin filaments underwent a parallel decrease in length. Using a sequential cytoskeletal extraction protocol and electron microscopy, we revealed in the present studies the coincident sequestration of a distinct, perinuclear pool of actin that was primarily absent in control cells. Actin sequestration progressed in a duration-dependent manner, occurring as early as 15 min of anoxia when cellular ATP dropped to <5% of control level. Phalloidin staining and depolymerization treatment showed the majority (>90%) of this sequestered actin to be F-actin. A microvillar actin bundling protein villin was also sequestered in the same perinuclear complex of anoxic proximal tubules. In conclusion, the present results demonstrate a coincident microvillar actin bundle disruption and the perinuclear sequestration of F-actin in ATP-depleted proximal tubular cells.

scholarly journals The effect of proteinuria-mediated endothelin-1 downregulation of PKCα signalling in proximal tubular cells and its successful/INS; treatment is measurable using microRNA15a as biomarker in vitro and in vivo

Life Sciences ◽  
2013 ◽  
Vol 93 (25-26) ◽  
pp. e5-e6
Author(s):  
Heike Loeser ◽  
Melanie von Brandenstein ◽  
Maike Wittersheim ◽  
Volker Burst ◽  
Claudia Richter ◽  
...  
Keyword(s):  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Endothelin 1 ◽  
Proximal Tubular

scholarly journals Advanced Oxidation Protein Products Induce Hypertrophy and Epithelial-To-Mesenchymal Transition in Human Proximal Tubular Cells through Induction of Endoplasmic Reticulum Stress

2015 ◽  
Vol 35 (2) ◽  
pp. 816-828 ◽  
Author(s):  
Xun Tang ◽  
Guang Rong ◽  
Yang Bu ◽  
Shaojie Zhang ◽  
Min Zhang ◽  
...  
Keyword(s):  
Protein Expression ◽  
Er Stress ◽  
Total Protein ◽  
Epithelial To Mesenchymal Transition ◽  
Proximal Tubular Cells ◽  
Advanced Oxidation Protein Products ◽  
Mesenchymal Transition ◽  
Tubular Cells ◽  
Cell Hypertrophy ◽  
Proximal Tubular

Background: In chronic kidney disease (CKD), the accumulation of advanced oxidation protein products (AOPPs) is prevalent. Hypertrophy and epithelial-to-mesenchymal transition (EMT) of tubular cells are associated with the pathogenesis of CKD. However, whether AOPPs induce tubular-cell hypertrophy and EMT is unclear. In this study, we investigated the effect of AOPPs on human proximal tubular cells (HK-2 cells) and the mechanisms underlying tubular-cell hypertrophy and EMT in vitro. Methods: The mRNA and protein expression of CCAAT/enhancer-binding protein-homologous protein (CHOP), glucose-regulated protein (GRP) 78, p27, α-smooth muscle actin (α-SMA) and E-cadherin were evaluated by quantitative real-time PCR and western blot, respectively. Cell cycle was detected by flow cytometry. Bicinchoninic acid method was performed to measure total protein content. Results: AOPP treatment upregulated total protein expression, caused an increase in the percentage of G1-phase cells, and induced the overexpression of p27 and α-SMA, lowered the expression of E-cadherin. Furthermore, AOPP treatment induced the overexpression of GRP78 and CHOP. Moreover, the aforementioned effects were reversed following the treatment of cells with an NADPH oxidase inhibitor, a reactive oxygen species (ROS) scavenger, or salubrinal, which is an inhibitor of ER stress, whereas these effects were produced after exposure to thapsigargin, an inducer of ER stress. Conclusion: Our results suggest that AOPPs induced HK-2-cell hypertrophy and EMT by inducing ER stress, which was likely mediated by ROS. These findings could facilitate the development of novel therapeutic strategies for suppressing the progression of CKD.

Indoxyl sulfate upregulates renal expression of ICAM-1 via production of ROS and activation of NF-κB and p53 in proximal tubular cells

Life Sciences ◽  
2013 ◽  
Vol 92 (2) ◽  
pp. 143-148 ◽  
Author(s):  
Hidehisa Shimizu ◽  
Maimaiti Yisireyili ◽  
Yukihiro Higashiyama ◽  
Fuyuhiko Nishijima ◽  
Toshimitsu Niwa
Keyword(s):  
Indoxyl Sulfate ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Renal Expression
Sign in / Sign up

Export Citation Format

Share Document