scholarly journals mTOR contributes to ER stress and associated apoptosis in renal tubular cells

2015 ◽  
Vol 308 (3) ◽  
pp. F267-F274 ◽  
Author(s):  
Guie Dong ◽  
Yu Liu ◽  
Lei Zhang ◽  
Shuang Huang ◽  
Han-Fei Ding ◽  
...  
Keyword(s):  
Er Stress ◽  
Kidney Diseases ◽  
Renal Diseases ◽  
Therapeutic Effects ◽  
Tubular Cells ◽  
Tunicamycin Treatment ◽  
Renal Tubular Cells ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular ◽  
Induced Apoptosis

ER stress has been implicated in the pathogenesis of both acute and chronic kidney diseases. However, the molecular regulation of ER stress in kidney cells and tissues remains poorly understood. In this study, we examined tunicamycin-induced ER stress in renal proximal tubular cells (RPTC). Tunicamycin induced the phosphorylation and activation of PERK and eIF2α within 2 h in RPTC, which was followed by the induction of GRP78 and CHOP. Consistently, tunicamycin also induced apoptosis in RPTC. Interestingly, mTOR was activated rapidly during tunicamycin treatment, as indicated by phosphorylation of both mTOR and p70S6K. Inhibition of mTOR with rapamycin partially suppressed the phosphorylation of PERK and eIF2a and the induction of CHOP and GRP78 induction during tunicamycin treatment. Rapamycin also inhibited apoptosis during tunicamycin treatment and increased cell survival. Collectively, the results suggest that mTOR plays a regulatory role in ER stress, and inhibition of mTOR may have potential therapeutic effects in ER stress-related renal diseases.

Activation of liver X receptors inhibits cadmium-induced apoptosis of human renal proximal tubular cells

2015 ◽  
Vol 236 (3) ◽  
pp. 145-153 ◽  
Author(s):  
Somsak Fongsupa ◽  
Sirima Soodvilai ◽  
Chatchai Muanprasat ◽  
Varanuj Chatsudthipong ◽  
Sunhapas Soodvilai
Keyword(s):  
Liver X Receptors ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular ◽  
X Receptors ◽  
Induced Apoptosis

Abstract 210: Stem Cell Conditioned Culture Media Attenuated Albumin-induced Epithelial-mesenchymal Transition in Renal Tubular Cells

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Junping Hu ◽  
Weiqing Han ◽  
Qing Zhu ◽  
Pin-Lan Li ◽  
Ningjun Li
Keyword(s):  
Epithelial Mesenchymal Transition ◽  
Culture Media ◽  
Mesenchymal Transition ◽  
Tubular Cells ◽  
Protein Levels ◽  
Renal Tubular Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular ◽  
Renal Tubular

Mesenchymal stem cells (MSCs) have been shown to be a promising therapy for many different diseases. Stem cell conditioned culture media (SCM) exhibit similar beneficial effects as MSCs. Albuminuria-induced epithelial-mesenchymal transition (EMT) plays an important role in progressive renal tubulointerstitial fibrosis in chronic renal disease. The present study tested the hypothesis that SCM inhibit albumin-induced EMT in cultured renal tubular cells. SCM were obtained by culturing rat adult MSCs for 3 days. Cultured renal proximal tubular cells were incubated with rat albumin (20μg/ml) and treated with SCM or control culture media. Our results showed that 48 h albumin incubation stimulated EMT in renal proximal tubular cells as shown by significant decrease in the protein levels of epithelial marker E-cadherin from 2.30 ± 0.27 to 0.87 ± 0.11 ( P < 0.05) and increase in the protein levels of mesenchymal marker fibroblast-specific protein 1 (FSP-1) (2.18±0.33 folds, P < 0.05). SCM treatment significantly inhibited these albumin-induced changes in E-cadherin and FSP-1 by 2.33±0.17 and 1.95±0.23 folds ( P < 0.05), respectively. Meanwhile, albumin increased the mRNA levels of pro-inflammatory factor monocyte chemoattractant protein-1 (MCP)-1 by nearly 30 folds compared with control. SCM almost abolished the increase of MCP-1 induced by albumin. Furthermore, Western blot results displayed that albumin rapidly decreased the cytosolic levels and increased the nuclear levels of NF-κB, indicating a translocation of NF-κB; immunofluorescence microscopy also demonstrated that albumin induced NF-κB translocation from the cytosol into nucleus. SCM blocked the translocation of NF-κB into nucleus. These results suggest that SCM attenuated albumin-induced EMT in renal tubular cells via inhibiting NF-κB activation and inflammation, which may serve as a new therapeutic approach for chronic kidney diseases. (Supported by NIH grant HL89563 and HL106042)

A tubule cell model for ifosfamide nephrotoxicity

2005 ◽  
Vol 83 (6) ◽  
pp. 499-508 ◽  
Author(s):  
Katarina Aleksa ◽  
Naomi Halachmi ◽  
Shinya Ito ◽  
Gideon Koren
Keyword(s):  
Cell Model ◽  
Tubule Cell ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Cyp Enzymes ◽  
Affect Cell Viability ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular ◽  
Renal Tubular ◽  
Pharmacological Method

Mechanisms leading to ifosfamide (IF)-induced renal damage have not been fully elucidated. Recent work suggests that localized renal tubular metabolism of IF and the production of the nephrotoxic chloroacetaldehyde may lead to nephrotoxicity. Presently no pharmacological method to reduce IF nephrotoxicity has been identified. The objectives of this study were to establish a tubule cell model for IF nephrotoxicity, to verify whether renal proximal tubular cells have the necessary cytochrome P450 (CYP) enzymes to oxidize IF, and whether they can metabolize IF to chloroacetaldehyde. CYP3A, and 2B mRNA and protein were identified in LLCPK-1 cells. The cells metabolized the R- and S-IF enantiomers to their respective 2- and 3-dechloroethylifosfamide metabolites, by-products of chloroacetal dehyde formation. Metabolite production was both time and concentration-dependent. IF did not affect cell viability. In contrast, glutathione-depleted cells showed time and dose-dependent damage. The presence of the relevant CYP enzymes in renal tubular cells along with their ability to metabolize IF to its 2- and 3-dechloroethylifosfamide metabolites suggests that nephrotoxic damage may result from the localized production of chloroacetaldehyde. Glutathione is a major defence mechanism against IF toxicity, thus pharmacological methods for replenishing intracellular glutathione may be effective in modulating IF-induced nephrotoxicity. Key words: LLCPK-1, metabolism, ifosfamide, renal, CYP3A, CYP2B.

F-actin disorganization in apoptotic cell death of cultured rat renal proximal tubular cells

1996 ◽  
Vol 270 (4) ◽  
pp. F593-F603 ◽  
Author(s):  
B. Van de Water ◽  
M. Kruidering ◽  
J. F. Nagelkerke
Keyword(s):  
Apoptotic Cell ◽  
Dna Fragments ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Lactate Dehydrogenase Release ◽  
Fragmented Nucleus ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular ◽  
Induced Apoptosis

The mechanism of nephrotoxin-induced apoptosis was studied in rat renal proximal tubular cells (PTC) exposed to the nephrotoxin S-(1,2-dichlorovinyl)-L-cysteine (DCVC). After a 6-h incubation, DCVC caused a condensation of heterochromatin and a fragmentation of the nucleus in 84 and 16% of the cells, respectively, which is indicative of apoptosis. This was confirmed biochemically by agarose gel electrophoresis demonstrating the formation of DNA fragments with multiples of 200 bp. The antioxidant N,N'-diphenyl-p-phenylenediamine prevented neither the fragmentation of the nucleus nor the formation of DNA fragments, but it did prevent lactate dehydrogenase release and bleb formation by DCVC. Apoptosis induced by DCVC was closely associated with F-actin disorganization: every cell with a fragmented nucleus displayed completely disorganized F-actin, while cells with a normal nucleus still possessed at least some intact F-actin also induced apoptosis in PTC. Similarly, dithiothreitol, which damages F-actin in PTC, caused apoptosis of PTC. These data suggest a causal relationship between F-actin disorganization and apoptosis of PTC.

scholarly journals Pinostrobin attenuates colistin-induced apoptosis of human renal proximal tubular cells

2021 ◽  
Vol 48 (6) ◽  
pp. 549-556
Author(s):  
Nichakorn Worakajit ◽  
Penjai Thongnuanjan ◽  
Napason Chabang ◽  
Sirima Soodvilai ◽  
Patoomratana Tuchinda ◽  
...  
Keyword(s):  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Proximal Tubular ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular ◽  
Induced Apoptosis

scholarly journals Sodium-dependent phosphate cotransporter type 1 sequence polymorphisms in male patients with gout

2009 ◽  
Vol 69 (6) ◽  
pp. 1232-1234 ◽  
Author(s):  
Wako Urano ◽  
Atsuo Taniguchi ◽  
Naohiko Anzai ◽  
Eisuke Inoue ◽  
Yoshikatsu Kanai ◽  
...  
Keyword(s):  
Nucleotide Polymorphisms ◽  
Proximal Tubular Cells ◽  
Tubular Cells ◽  
Renal Tubular Cells ◽  
Sodium Dependent ◽  
Proximal Tubular ◽  
Male Patients ◽  
Renal Proximal Tubular Cells ◽  
Renal Proximal Tubular

ObjectivesMolecular biological approaches have recently identified urate transporters in renal proximal tubular cells. Human sodium-dependent phosphate cotransporter type 1 encoded by SLC17A1 is a urate transporter localised to the renal proximal tubular cells and candidate molecule to secret urate from renal tubular cells to urine. This study investigated the roles of SLC17A1 in the development of gout.Patients and MethodsSingle nucleotide polymorphisms in the human SLC17A1 gene (rs1165176, rs1165151, rs1165153, rs1165196, rs1165209, rs1165215, rs1179086, rs3799344 and rs3757131) were selected, and an association study was conducted using male patients with gout (n=175) and male controls (n=595).ResultsThere were significant differences between gout and control groups in the distribution of genotypes at rs1165196 (T806C; Ile269Thr, odds ratio (OR) 0.55, p=0.0035), rs1179086 (OR 0.57, p=0.0018) and rs3757131 (OR 0.54, p=0.0026). In controls, T806C alone had no effect on serum uric acid (sUA) levels. However, T806C showed significant interaction with a reduction of sUA in obese individuals (body mass index ≥25) using multiple regression analysis.ConclusionsOur data suggest that SLC17A1 polymorphisms are associated with the development of gout.

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