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Mitogen‐Activated Protein Kinases Differentially Regulate Renal Cell Paracellular Permeability
Author(s) -
Watari Jessica,
Axis Josephine,
Jaggi Shirin,
Voronina Angelina,
Amsler Kurt
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.lb686
Subject(s) - paracellular transport , occludin , mapk/erk pathway , chemistry , microbiology and biotechnology , tight junction , kinase , permeability (electromagnetism) , biology , biochemistry , membrane
Movement of compounds between renal epithelial cells, paracellular permeability, is mediated primarily by the permeability of the circumferential tight junction structure (TJ) located at the apicolateral border of adjacent epithelial cells. Hydrogen peroxide (H 2 O 2 ), which contributes to renal ischemia‐reperfusion injury, increased the paracellular permeability of two renal epithelial cell lines, MDCK (distal tubule) and LLC‐PK 1 (proximal tubule), in a concentration‐dependent manner. H 2 O 2 treatment also produced a concentration‐dependent increase in the phosphorylation of the Mitogen‐Activated Protein Kinases ERK 1/2, JNK 1/2, and p38MAPK. Pretreatment of renal cell populations with inhibitors of ERK 1/2 activation (U0126, PD98059) and p38MAPK activity (SB202190), diminished or completely blocked the ability of H 2 O 2 to increase paracellular permeability. In contrast, treatment with two JNK 1/2 inhibitors, SP600125 and AS601245, did not block the ability of H 2 O 2 to increase renal paracellular permeability. In fact, treatment with JNK 1/2 inhibitors increased paracellular permeability in a concentration‐dependent manner when added alone and augmented the increase in paracellular permeability when added prior to H 2 O 2 treatment. Previous studies demonstrated that treatment of renal epithelial cells with H 2 O 2 slowed the movement of GFP‐occludin into the TJ region, as measured by Fluorescence Recovery After Photobleaching. Treatment of cell populations with U0126 alone slowed the movement of GFP‐occludin into the TJ region. In U0126‐treated cell populations, however, H 2 O 2 treatment was unable to slow further the rate of GFP‐occludin movement into the TJ region. These results indicate: 1) H 2 O 2 treatment increases renal epithelial paracellular permeability via activation of ERK 1/2 and p38MAPK; 2) Steady state JNK 1/2 activity may promote maintenance of the paracellular permeability barrier; and 3) The ability of H 2 O 2 to modulate the mobility of occludin into the TJ structure may be associated with its ability to increase renal cell paracellular permeability. Support or Funding Information Research supported by NIH grant R15 DK091749