Premium
ERK 1/2 Mediates H 2 O 2 ‐Induced Increase in Renal Epithelial Paracellular Permeability
Author(s) -
Jaggi Shirin,
Voronina Angelina,
Axis Josephine,
Amsler Kurt
Publication year - 2015
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.29.1_supplement.673.4
Subject(s) - paracellular transport , mapk/erk pathway , chemistry , microbiology and biotechnology , permeability (electromagnetism) , cytotoxicity , kinase , phosphorylation , tight junction , biophysics , biochemistry , biology , in vitro , membrane
The paracellular permeability of renal epithelia is determined primarily by the integrity of the tight junction (TJ) structure located at the apicolateral borders of adjacent epithelial cells. Treatment of confluent populations of MDCK cells (distal tubule‐like) and LLC‐PK 1 cells (proximal tubule‐like) with hydrogen peroxide (H 2 O 2 ) increases the paracellular permeability to large solutes in a concentration‐dependent manner. H 2 O 2 was cytotoxic at higher concentrations. We have examined the involvement of Mitogen‐Activated Protein Kinases (MAPKs) in mediating these H 2 O 2 actions. Treatment with H 2 O 2 increased the phosphorylation (activation) of multiple MAPKs, ERK ½, JNK ½, and p38MAPK, in a time‐dependent manner. Phosphorylation of each MAPK peaked at 10‐30 minutes and declined by 120 minutes. Pretreatment of cells with U0126 or PD98059, inhibitors of ERK ½ activation, blocked the ability of H 2 O 2 to increase paracellular permeability. SB202190, a p38MAPK inhibitor, diminished but did not entirely block the H 2 O 2 effect. Treatment of cells with SP600125, an inhibitor of JNK ½ activation, did not affect the ability of H 2 O 2 to increase paracellular permeability. Pretreatment with U0126 and SB202190, but not SP600125, also diminished the cytotoxicity observed at higher H 2 O 2 concentrations. These results indicate that MAPKs, in particular ERK ½, have a central role in mediating the effects of H 2 O 2 on both modulation of paracellular permeability and induction of cytotoxicity in renal epithelial cells. (supported by NIH 1R15DK091749)