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Metabolites of the phospholipase D pathway regulate H 2 O 2 ‐induced filamin redistribution in endothelial cells
Author(s) -
Hastie Laurie E.,
Patton Wayne F.,
Hechtman Herbert B.,
Shepro David
Publication year - 1998
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(19980315)68:4<511::aid-jcb10>3.0.co;2-c
Subject(s) - filamin , phosphatidylinositol , microbiology and biotechnology , cytoskeleton , intracellular , cytosol , second messenger system , gelsolin , phosphatidic acid , phospholipase d , phospholipase c , phospholipase a2 , chemistry , biology , biochemistry , actin , signal transduction , phospholipid , cell , enzyme , membrane
Hypoxia/reoxygenation injury to cultured endothelial cells results in cytoskeletal rearrangement and second messenger activation related to increased monolayer junctional permeability. Cytoskeletal rearrangement by reactive oxygen species may be related to specific activation of the phospholipase D (PLD) pathway. Human umbilical vein endothelial cell monolayers are exposed to H 2 O 2 (100 μM) or metabolites of the PLD pathway for 1–60 min. Changes in cAMP levels, Ca 2+ levels, PIP 2 production, filamin distribution, and intercellular gap formation are then quantitated. H 2 O 2 ‐induced filamin translocation from the membrane to the cytosol occurs after 1‐min H 2 O 2 treatment, while intercellular gap formation significantly increases after 15 min. H 2 O 2 and phosphatidic acid exposure rapidly decrease intracellular cAMP levels, while increasing PIP 2 levels in a Ca 2+ ‐independent manner. H 2 O 2 ‐induced cAMP decreases are prevented by inhibiting phospholipase D. H 2 O 2 ‐induced cytoskeletal changes are prevented by inhibiting phospholipase D, phosphatidylinositol‐4‐phosphate kinase, phosphoinositide turnover, or by adding a synthetic peptide that binds PIP 2 . These data indicate that metabolites produced downstream of H 2 O 2 ‐induced PLD activation may mediate filamin redistribution and F‐actin rearrangement. J. Cell. Biochem. 68:511–524, 1998. © 1998 Wiley‐Liss, Inc.