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

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Kuan-Yu Hung ◽  
Shin-Yun Liu ◽  
Te-Cheng Yang ◽  
Tien-Ling Liao ◽  
Shu-Huei Kao
Keyword(s):  
Cell Death ◽  
Mitochondrial Dysfunction ◽  
Mesothelial Cells ◽  
Cytochrome C Release ◽  
Dialysis Adequacy ◽  
Peritoneal Mesothelial Cells ◽  
Functional Changes ◽  
Key Factor ◽  
Human Peritoneal Mesothelial Cells ◽  
Induced Apoptosis

Human peritoneal mesothelial cells (HPMCs) are a critical component of the peritoneal membrane and play a pivotal role in dialysis adequacy. Loss of HPMCs can contribute to complications in peritoneal dialysis. Compelling evidence has shown that high-dialysate glucose is a key factor causing functional changes and cell death in HPMCs. We investigated the mechanism of HPMC apoptosis induced by high-dialysate glucose, particularly the role of mitochondria in the maintenance of HPMCs. HPMCs were incubated at glucose concentrations of 5 mM, 84 mM, 138 mM, and 236 mM. Additionally, N-acetylcysteine (NAC) was used as an antioxidant to clarify the mechanism of high-dialysate-glucose-induced apoptosis. Exposing HPMCs to high-dialysate glucose resulted in substantial apoptosis with cytochrome c release, followed by caspase activation and poly(ADP-ribose) polymerase cleavage. High-dialysate glucose induced excessive reactive oxygen species production and lipid peroxidation as well as oxidative damage to DNA. Mitochondrial fragmentation, multiple mitochondrial DNA deletions, and dissipation of the mitochondrial membrane potential were also observed. The mitochondrial dysfunction and cell death were suppressed using NAC. These results indicated that mitochondrial dysfunction is one of the main causes of high-dialysate-glucose-induced HPMC apoptosis.

Expression of Aquaporin-1 in Human Peritoneal Mesothelial Cells and Its Upregulation by GlucoseIn Vitro

2001 ◽  
Vol 12 (5) ◽  
pp. 1036-1045 ◽  
Author(s):  
KAR NENG LAI ◽  
FU KEUNG LI ◽  
HAO YUI LAN ◽  
SYDNEY TANG ◽  
ANITA W. L. TSANG ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Peritoneal Dialysis ◽  
Mesothelial Cells ◽  
Dependent Manner ◽  
Peritoneal Membrane ◽  
Dialysis Adequacy ◽  
Peritoneal Mesothelial Cells ◽  
Aqp1 Expression ◽  
Human Peritoneal Mesothelial Cells ◽  
Osmotic Agents

Abstract. Aquaporin (AQP) is a family of water channels that are highly selective for the passage of water and occasionally glycerol. In previous studies, only AQP1 was found in human peritoneal endothelial cells in both control subjects and patients on peritoneal dialysis. As human peritoneal mesothelial cells (HPMC) play an important role in dialysis adequacy and fluid balance in continuous ambulatory peritoneal dialysis patients, this study examined whether AQP1 is present in HPMC. It was found that AQP1 mRNA and protein are present in HPMC constitutively. The localization of AQP1 protein in peritoneal mesothelial cells was confirmed by double immunohistochemical staining of the mesothelial lining of human peritoneal membrane. More important, the expression of AQP1 in HPMC is not constitutive and the transcription and biosynthesis of AQP1 in HPMC is inducible by osmotic agents such as glucose and mannitol. There was significant enhancement of AQP1 biosynthesis upon exposure to glucose in a time- and dose-dependent manner (P< 0.0001). Similar findings were observed in the AQP1 biosynthesis by an endothelial cell line, EA.hy 926. Of particular interest, the upregulation in AQP1 mRNA or biosynthesis in mesothelial cells was always significantly higher than that of endothelial cells when the experiments were conducted under identical settings (P< 0.001). AQP1 expression in HPMC was demonstrated for the first time. Osmotic agents upregulate both mRNA and protein expression of this aquaporin. The role of AQP1 in HPMC in maintaining the ultrafiltration of the peritoneal membrane is potentially of clinical interest.

scholarly journals Staphylococcus aureus induces caspase-independent cell death in human peritoneal mesothelial cells

2006 ◽  
Vol 70 (6) ◽  
pp. 1089-1098 ◽  
Author(s):  
B. Haslinger-Löffler ◽  
B. Wagner ◽  
M. Brück ◽  
K. Strangfeld ◽  
M. Grundmeier ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Cell Death ◽  
Mesothelial Cells ◽  
Peritoneal Mesothelial Cells ◽  
Human Peritoneal Mesothelial Cells

Alpha-1 antitrypsin inhibits formaldehyde-induced apoptosis of human peritoneal mesothelial cells

2020 ◽  
Vol 40 (2) ◽  
pp. 124-131 ◽  
Author(s):  
Jeong-Hoon Lim ◽  
Sang Mi Park ◽  
Ju-Min Yook ◽  
Ji-Sun Ahn ◽  
Soon-Youn Choi ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Caspase 3 ◽  
Cysteine Proteases ◽  
Mesothelial Cells ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Peritoneal Mesothelial Cells ◽  
Human Peritoneal Mesothelial Cells ◽  
Alpha 1 Antitrypsin ◽  
Induced Apoptosis ◽  
Mtt Assays

Background: The alpha-1 antitrypsin (AAT) protein has an important role in the anti-inflammatory and apoptotic response. AAT inhibits not only serine proteases but also cysteine and aspartic proteases. Apoptosis results from the sequential activation of cysteine proteases of the caspase family. This study aimed to evaluate the effect of AAT on formaldehyde-induced apoptosis of human peritoneal mesothelial cells (HPMCs). Methods: HPMCs were cultured and treated with formaldehyde (250 µM) to induce apoptosis. In the AAT group, the cultured HPMCs were pretreated with AAT (2 mg/mL) for 1 h before formaldehyde treatment. We used 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays to determine cell viability, and flow cytometry and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) assays to detect apoptosis. The MTT assays were used to find optimal concentrations of formaldehyde and AAT. We measured caspase-3 activity and used Western blotting to estimate Bcl-2 and Bad expression. Results: Flow cytometry and TUNEL assays revealed that formaldehyde exposure significantly increased apoptosis compared with the control treatment, but pretreatment with AAT significantly inhibited this effect. Compared with the control, caspase-3 activity was significantly increased and the ratio of Bcl-2 to Bad expression significantly decreased following treatment with formaldehyde. However, caspase-3 activity was significantly lower and the Bcl-2 to Bad expression ratio higher in the AAT group than in the formaldehyde-only group. Conclusion: AAT inhibits formaldehyde-induced apoptosis of HPMCs via a caspase-mediated pathway. These data support a potential use for AAT as a therapeutic agent for the inhibition of peritoneal cell apoptosis during peritoneal dialysis.

Phosphate-Induced Apoptosis in Human Peritoneal Mesothelial Cells in vitro

2011 ◽  
Vol 34 (1) ◽  
pp. 77-86 ◽  
Author(s):  
Jong-Won Park ◽  
Ju-Min Yook ◽  
Hye-Myung Ryu ◽  
Soon-Youn Choi ◽  
Masayo Morishita ◽  
...  
Keyword(s):  
Mesothelial Cells ◽  
Peritoneal Mesothelial Cells ◽  
Human Peritoneal Mesothelial Cells ◽  
Induced Apoptosis

Staphylococcal infections impair the mesothelial fibrinolytic system: The role of cell death and cytokine release

2007 ◽  
Vol 98 (10) ◽  
pp. 813-822 ◽  
Author(s):  
Michaela Brück ◽  
Matthias Grundmeier ◽  
Georg Peters ◽  
Bhanu Sinha ◽  
Bettina Haslinger-Löffler
Keyword(s):  
Cell Death ◽  
Adhesion Molecules ◽  
Mononuclear Cells ◽  
Critical Role ◽  
Mesothelial Cells ◽  
Fibrinolytic System ◽  
Peritoneal Fibrosis ◽  
Peritoneal Mesothelial Cells ◽  
System Components ◽  
Human Peritoneal Mesothelial Cells

SummaryBacterial peritonitis is a serious complication of peritoneal dialysis patients and of patients after abdominal surgery. Especially episodes due to Staphylococcus aureus can harm the peritoneum severely, resulting in peritoneal fibrosis. Human peritoneal mesothelial cells play a critical role in maintaining the integrity of the peritoneum, as they release components of the fibrinolytic system and regulate the influx of immune cells by expressing chemokines and adhesion molecules. Using cultured human peritoneal mesothelial cells (HMCs) and blood mononuclear cells,we analyzed the effect of different staphylococcal strains on mesothelial fibrinolysis and on inflammatory reactions and show that only S. aureus strains with an invasive and hemolytic phenotype decrease the production of fibrinolytic system components, most likely via cell death induction. Furthermore, HMCs react to invading staphylococci by enhanced expression of chemokines and adhesion molecules. Mononuclear cells were activated by all staphylococcal strains tested, and their culture supernatants impaired mesothelial fibrinolysis. Simvastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, efficiently enhanced the mesothelial fibrinolytic capacity under these inflammatory conditions, but did not protect HMCs against S. aureus-induced cell death. We conclude that only selected S. aureus strains decrease the release of fibrinolytic system components and provoke a mesothelial inflammatory response. These factors most likely contribute to peritoneal fibrosis and might account for the severe clinical presentation of S. aureus peritonitis.

Mitochondrial dysfunction is an early event in high-NaCl-induced apoptosis of mIMCD3 cells

2002 ◽  
Vol 282 (6) ◽  
pp. F981-F990 ◽  
Author(s):  
Luis Michea ◽  
Christian Combs ◽  
Peter Andrews ◽  
Natalia Dmitrieva ◽  
Maurice B. Burg
Keyword(s):  
Mitochondrial Dysfunction ◽  
Collecting Duct ◽  
Early Event ◽  
Mitochondrial Morphology ◽  
Cytochrome C Release ◽  
Activity Increase ◽  
Transmission Electron ◽  
Mitochondrial Membrane Depolarization ◽  
Medullary Collecting Duct ◽  
Induced Apoptosis

Raising osmolality to 700 mosmol/kgH2O by the addition of NaCl rapidly kills most murine inner renal medullary collecting duct cells (mIMCD3), but they survive at 500 mosmol/kgH2O. At 300 and 500 mosmol/kgH2O, NADH autofluorescence is present in a mitochondria-associated, punctate perinuclear pattern. Within 45 s to 30 min at 700 mosmol/kgH2O, the autofluorescence spreads diffusely throughout the cell. This correlates with mitochondrial membrane depolarization, measured as decreased tetramethylrhodamine methyl ester perchlorate (TMRM) fluorescence. Mitochondrial dysfunction should increase the cellular ADP/ATP ratio. In agreement, this ratio increases within 1–6 h. Mitochondrial morphology (transmission electron microscopy) is unaffected, but nuclear hypercondensation becomes evident. Progressive apoptosis occurs beginning 1 h after osmolality is raised to 700, but not to 500, mosmol/kgH2O. General caspase activity and caspase-9 activity increase only after 6 h at 700 mosmol/kgH2O. The mitochondrial Bcl-2/Bax ratio decreases within 1–3 h, but no cytochrome c release is evident. The mitochondria contain little p53 at any osmolality. Adding urea to 700 mosmol/kgH2O does not change NADH or TMRM fluorescence. We conclude that extreme acute hypertonicity causes a mitochondrial dysfunction involved in the initiation of apoptosis.

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