Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:3.6.4.1 (
myosin ATPase
)
1,140
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Hydrogen peroxide (H
2
O
2
) increases paracellular permeability of Madin-Darby canine kidney (MDCK) cells, but the mechanism mediating this effect remains unclear. Treatment of MDCK cells with H
2
O
2
activated ERK 1/2. Inhibition of ERK 1/2 activation blocked the ability of H
2
O
2
to increase paracellular permeability. Knockdown of zonula occludens-1 (ZO-1) protein but not occludin eliminated the ability of H
2
O
2
to increase paracellular permeability. H
2
O
2
treatment did not, however, affect the total cell content or contents of the Triton X-100-soluble and -insoluble fractions for occludin, ZO-1, or
ZO-2
. H
2
O
2
treatment decreased the number of F-actin stress fibers in the basal portion of the cells. Similar to wild-type MDCK cells, H
2
O
2
increased ERK 1/2 activation in ZO-1 knockdown and occludin knockdown cells. Inhibition of ERK 1/2 activation blocked the increase in paracellular permeability in occludin knockdown cells. ZO-1 knockdown cell paracellular permeability was regulated by PP1, an src inhibitor, indicating that the loss of response to H
2
O
2
was not a general loss of the ability to regulate the paracellular barrier. Inhibition of
myosin ATPase
activity with blebbistatin increased paracellular permeability in ZO-1 knockdown cells but not in wild-type MDCK cells. H
2
O
2
treatment sensitized wild-type MDCK cells to inhibition of
myosin ATPase
. Knockdown of TOCA-1 protein, which promotes formation of local branched actin networks, reproduced the effects of ZO-1 protein knockdown. These results demonstrate that H
2
O
2
increases MDCK cell paracellular permeability through activation of ERK 1/2. This H
2
O
2
action requires ZO-1 protein and TOCA-1 protein, suggesting involvement of the actin cytoskeleton.
...
PMID:ZO-1 protein is required for hydrogen peroxide to increase MDCK cell paracellular permeability in an ERK 1/2-dependent manner. 2987 7
