High-Dialysate-Glucose-Induced Oxidative Stress and Mitochondrial-Mediated Apoptosis in Human Peritoneal Mesothelial Cells

Hung, Kuan‐Yu; Liu, Shin Yun; Yang, Te; Liao, Tien Ling; Kao, Shu Huei

doi:10.1155/2014/642793

Cited by 36 publications

(41 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There have been several studies demonstrating the role of ROS in the development of peritoneal fibrosis [35,36] . High glucose and glucose-based PD solutions induced generation of ROS in cultured HPMCs [37–39] . Furthermore, treatment with antioxidants, NAC or catalase, effectively reversed high-glucose-induced change in E-cadherin and α-SMA [35] .…”

Section: Discussionmentioning

confidence: 97%

Effect of aldosterone on epithelial-to-mesenchymal transition of human peritoneal mesothelial cells

Shin

Lee

et al. 2015

Kidney Research and Clinical Practice

View full text Add to dashboard Cite

BackgroundPeritoneal fibrosis is one of the major causes of technical failure in patients on peritoneal dialysis. Epithelial-to-mesenchymal transition (EMT) of the peritoneum is an early and reversible mechanism of peritoneal fibrosis. Human peritoneal mesothelial cells (HPMCs) have their own renin–angiotensin–aldosterone system (RAAS), however, it has not been investigated whether aldosterone, an end-product of the RAAS, induces EMT in HPMCs, and which mechanisms are responsible for aldosterone-induced EMT.MethodsEMT of HPMCs was evaluated by comparing the expression of epithelial cell marker, E-cadherin, and mesenchymal cell marker, α-smooth muscle actin after stimulation with aldosterone (1–100nM) or spironolactone. Activation of extracellular signal-regulated kinase (ERK)1/2 and p38 mitogen-activated protein kinase (MAPK) and generation of reactive oxygen species (ROS) were assessed by western blotting and 2′,7′-dichlorofluororescein diacetate staining, respectively. The effects of MAPK inhibitors or antioxidants (N-acetyl cysteine, apocynin, and rotenone) on aldosterone-induced EMT were evaluated.ResultsAldosterone induced EMT in cultured HPMCs, and spironolactone blocked aldosterone-induced EMT. Aldosterone induced activation of both ERK1/2 and p38 MAPK from 1 hour. Either PD98059, an inhibitor of ERK1/2, or SB20358, an inhibitor of p38 MAPK, attenuated aldosterone-induced EMT. Aldosterone induced ROS in HPMCs from 5 minutes, and antioxidant treatment ameliorated aldosterone-induced EMT. N-acetyl cysteine and apocynin alleviated activation of ERK and p38 MAPK.ConclusionAldosterone induced EMT in HPMCs by acting through the mineralocorticoid receptor. Aldosterone-induced generation of ROS followed by activation of ERK, and p38 MAPK served as one of the mechanisms of aldosterone-induced EMT of HPMCs.

show abstract

Section: Discussionmentioning

confidence: 97%

Effect of aldosterone on epithelial-to-mesenchymal transition of human peritoneal mesothelial cells

Shin

Lee

et al. 2015

Kidney Research and Clinical Practice

View full text Add to dashboard Cite

show abstract

“…Mesothelial cell injury is the first step in the development of peritoneal fibrosis, later leading to sclerosis [ 8 , 9 ], with bio-incompatibility of the PD solution and toxic molecules playing a central role in the pathology [ 10 ]. These molecules include glucose and glucose degradation products (GDPs) in the PD solution [ 11 – 13 ], and exogenous oxidants, such as iron [ 14 , 15 ]. Recent histological studies have reported that the use of neutral PD solutions with low GDPs are beneficial in ameliorating histological changes in the membrane [ 16 , 17 ], although the risk of EPS remains an issue of serious concern, even in patients treated with neutral PD solutions [ 18 , 19 ].…”

Section: Introductionmentioning

confidence: 99%

Dissolved molecular hydrogen (H2) in Peritoneal Dialysis (PD) solutions preserves mesothelial cells and peritoneal membrane integrity

et al. 2017

View full text Add to dashboard Cite

BackgroundPeritoneal dialysis (PD) is used as renal replacement therapy in patients with end-stage kidney disease. However, peritoneal membrane failure remains problematic and constitutes a critical cause of PD discontinuation. Recent studies have revealed the unique biological action of molecular hydrogen (H2) as an anti-oxidant, which ameliorates tissue injury. In the present study, we aimed to examine the effects of H2 on the peritoneal membrane of experimental PD rats.MethodEight-week-old male Sprague-Dawley rats were divided into the following groups (n = 8–11 each) receiving different test solutions: control group (no treatment), PD group (commercially available lactate-based neutral 2.5% glucose PD solution), and H2PD group (PD solution with dissolved H2 at 400 ppb). Furthermore, the influence of iron (FeCl3: 5 μM: inducer of oxidative cellular injury) in the respective PD solutions was also examined (Fe-PD and Fe-H2PD groups). The H2PD solution was manufactured by bathing a PD bag in H2-oversaturated water created by electrolysis of the water. Twenty mL of the test solutions were intraperitoneally injected once a day for 10 days. Parietal peritoneum samples and cells collected from the peritoneal surface following treatment with trypsin were subjected to analysis.ResultsIn the PD group as compared to controls, a mild but significant sub-mesothelial thickening was observed, with increase in the number of cells in the peritoneal surface tissue that were positive for apoptosis, proliferation and vimentin, as seen by immunostaining. There were significantly fewer of such changes in the H2PD group, in which there was a dominant presence of M2 (CD163+) macrophages in the peritoneum. The Fe-PD group showed a significant loss of mesothelial cells with sub-mesothelial thickening, these changes being ameliorated in the Fe-H2PD group.ConclusionH2-dissolved PD solutions could preserve mesothelial cells and peritoneal membrane integrity in PD rats. Clinical application of H2 in PD could be a novel strategy for protection of peritoneal tissue during PD treatment.

show abstract

“…Since high glucose is known to be able to elicit cell injury via induction of oxidative stress [19, 20], we tested whether oxidative stress was involved in PDS-induced PMC injury. Using fluorescent probes for ROS and superoxide, we detected an increased fluorescence intensity in PDS-treated cells, reflecting an elevation in ROS and superoxide production (Fig.…”

Section: Resultsmentioning

confidence: 99%

Sulfotanshinone IIA Sodium Ameliorates Glucose Peritoneal Dialysis Solution-Induced Human Peritoneal Mesothelial Cell Injury via Suppression of ASK1-P38-mediated Oxidative Stress

Zhou

Sun

et al. 2018

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Long-term use of high-glucose peritoneal dialysis solution (PDS) induces peritoneal mesothelial cell (PMC) injury, peritoneal dysfunction, and peritoneal dialysis (PD) failure in patients with end-stage renal disease. How to preserve PMCs in PD is a major challenge for nephrologists worldwide. In this study, we aimed to elucidate the efficacy and mechanisms of sulfotanshinone IIA sodium (Tan IIa) in ameliorating high-glucose PDS-induced human PMC injury. Methods: The human PMC line HMrSV5 was incubated with 4.25% PDS in vitro to mimic the high-glucose conditions in PD. Cellular viability was measured by Cell Counting Kit 8. Generation of superoxide and reactive oxygen species (ROS) was assessed using a Total ROS/Superoxide Detection Kit. Oxidative modification of protein was evaluated by OxyBlot Protein Oxidation Detection Kit. TUNEL (dT-mediated dUTP nick end labeling) assay and DAPI (4,6-diamidino-2-phenylindole) staining were used to evaluate apoptosis. Western blot analysis was performed to evaluate the efficacy and mechanisms of Tan IIa. Results: Tan IIa protected PMCs against PDS-induced injury as evidenced by alleviating changes in morphology and loss of cell viability. Consistent with their antioxidant properties, N-acetyl-L-cysteine (NAC) and Tan IIa suppressed superoxide and ROS production, protein oxidation, and apoptosis elicited by PDS. Apoptosis signal-regulating kinase 1 (ASK1)-p38 signaling was activated by PDS. Both Tan IIa and NAC suppressed ASK1 and p38 phosphorylation elicited by PDS. Moreover, genetic downregulation of ASK1 ameliorated cell injury and inhibited the phosphorylation of p38 and activation of caspase 3. Conclusion: Tan IIa protects PMCs against PDS-induced oxidative injury through suppression of ASK1-p38 signaling.

show abstract

High-Dialysate-Glucose-Induced Oxidative Stress and Mitochondrial-Mediated Apoptosis in Human Peritoneal Mesothelial Cells

Cited by 36 publications

References 30 publications

Effect of aldosterone on epithelial-to-mesenchymal transition of human peritoneal mesothelial cells

Effect of aldosterone on epithelial-to-mesenchymal transition of human peritoneal mesothelial cells

Dissolved molecular hydrogen (H2) in Peritoneal Dialysis (PD) solutions preserves mesothelial cells and peritoneal membrane integrity

Sulfotanshinone IIA Sodium Ameliorates Glucose Peritoneal Dialysis Solution-Induced Human Peritoneal Mesothelial Cell Injury via Suppression of ASK1-P38-mediated Oxidative Stress

Contact Info

Product

Resources

About