Role of mitochondrial respiratory chain complex III in high glucose peritoneal dialysate-induced hyperpermeability of HPMCs

Xuejing Zhu, Guanghui Ling, Li Xiao, Yinhong Liu, Shaobin Duan, Youming Peng, Yashpal S. Kanwar, Lin Sun, Fuyou Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Background: High-glucose-based peritoneal dialysis solution (PDS) is considered to be one of the primary causes for the increase of ionic permeability in peritoneum as detected by transmesothelial electrical resistance (TER) measurements and claudin-1 expression. However, the mechanism is not clear. The aim of this study is to test the hypothesis that high-glucose PDS induces hyperpermeability in human peritoneal mesothelial cell (HPMC) monolayer by mitochondrial respiratory chain complex III pathway. Methods: HPMCs were cultured in a 1 : 1 mix of Dulbecco's modified Eagle's medium (DMEM) and PDS containing 1.5 and 4.25 glucose for 24 h. A 1 : 1 mixture of 160 mgL glutathione and 4.25 glucose PDS was also added as an antioxidant group. TER measurement and immunostaining and western blot analysis of claudin-1 expression were examined for detection of permeability damage in HPMCs. MitoSOX™ Red staining and respiratory chain complexes' activities were determined for detection of mitochondrial reactive oxygen species (ROS) production and mitochondrial complexes' activities. Results: TER decreased in a time- and concentration-dependent manner after culture with high-glucose PDS for 24 h. Claudin-1 was also downregulated. Complex III activity was inhibited accompanied by increasing mitochondrial ROS generation. These changes were partially prevented by glutathione. Conclusion: These findings demonstrate that mitochondrial respiratory complex III pathway has crucial importance in maintaining permeability of HPMCs, which might reveal a valuable target for novel therapies to fight hyperpermeability of peritoneum during the prolonged PD treatment.

Original languageEnglish (US)
Pages (from-to)1103-1108
Number of pages6
JournalRenal Failure
Volume32
Issue number9
DOIs
StatePublished - 2010

Keywords

  • human peritoneal mesothelial cell
  • mitochondria
  • peritoneal dialysis
  • permeability
  • respiratory chain complex

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine
  • Nephrology

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