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Exocyst Sec10 protects epithelial barrier integrity and enhances recovery following oxidative stress, by activation of the MAPK pathway
- Source :
- American Journal of Physiology-Renal Physiology. 298:F818-F826
- Publication Year :
- 2010
- Publisher :
- American Physiological Society, 2010.
-
Abstract
- Cell-cell contacts are essential for epithelial cell function, and disruption is associated with pathological conditions including ischemic kidney injury. We hypothesize that the exocyst, a highly-conserved eight-protein complex that targets secretory vesicles carrying membrane proteins, is involved in maintaining renal epithelial barrier integrity. Accordingly, increasing exocyst expression in renal tubule cells may protect barrier function from oxidative stress resulting from ischemia and reperfusion (I/R) injury. When cultured on plastic, Madin-Darby canine kidney (MDCK) cells overexpressing Sec10, a central exocyst component, formed domes showing increased resistance to hydrogen peroxide (H2O2). Transepithelial electric resistance (TER) of Sec10-overexpressing MDCK cells grown on Transwell filters was higher than in control MDCK cells, and the rate of TER decrease following H2O2 treatment was less in Sec10-overexpressing MDCK cells compared with control MDCK cells. After removal of H2O2, TER returned to normal more rapidly in Sec10-overexpressing compared with control MDCK cells. In collagen culture MDCK cells form cysts, and H2O2 treatment damaged Sec10-overexpressing MDCK cell cysts less than control MDCK cell cysts. The MAPK pathway has been shown to protect animals from I/R injury. Levels of active ERK, the final MAPK pathway step, were higher in Sec10-overexpressing compared with control MDCK cells. U0126 inhibited ERK activation, exacerbated the H2O2-induced decrease in TER and cyst disruption, and delayed recovery of TER following H2O2 removal. Finally, in mice with renal I/R injury, exocyst expression decreased early and returned to normal concomitant with functional recovery, suggesting that the exocyst may be involved in the recovery following I/R injury.
- Subjects :
- Male
MAPK/ERK pathway
Time Factors
MAP Kinase Signaling System
Physiology
Vesicular Transport Proteins
Exocyst
Biology
Kidney
Transfection
medicine.disease_cause
Permeability
Cell Line
Mice
Enzyme activator
Dogs
Nitriles
Butadienes
Electric Impedance
medicine
Animals
Humans
Phosphorylation
Extracellular Signal-Regulated MAP Kinases
Protein Kinase Inhibitors
Membrane Proteins
Epithelial Cells
Hydrogen Peroxide
Articles
Oxidants
medicine.disease
Epithelium
Cell biology
Enzyme Activation
Mice, Inbred C57BL
Oxidative Stress
medicine.anatomical_structure
Creatinine
Reperfusion Injury
Mitogen-activated protein kinase
Immunology
biology.protein
Carrier Proteins
Reperfusion injury
Oxidative stress
Subjects
Details
- ISSN :
- 15221466 and 1931857X
- Volume :
- 298
- Database :
- OpenAIRE
- Journal :
- American Journal of Physiology-Renal Physiology
- Accession number :
- edsair.doi.dedup.....8baf6b3a68a7a2b26b2741c2dc5207db