Abstract
Increasing evidence indicates that phospholipid oxidation plays important roles in atherosclerosis. Here, we investigated the involvement of Rho-family GTPases inphosphatidylcholine hydroperoxide (PCOOH)-induced THP-1 cell adhesion to ICAM-1. Isoprenoid depletion by fluvastatin and geranylgeranyltransferase inhibition by GGTI-286 suppressed PCOOH-induced cell adhesion to ICAM-1 and F-actin-rich membrane protrusion formation. Pull-down assays demonstrated the activation of Rac1 and Rac2 in PCOOH-treated cells. Pan-Rho-family GTPase inhibitor Clostridium difficile toxin B, Rac-specific inhibitor NSC23776, and RNA interference of the Rac isoforms suppressed the cell adhesion. These findings indicate the involvement of Rac GTPase activation in PCOOH-induced cell adhesion to ICAM-1 via actin reorganization.
Copyright © 2011 Elsevier Inc. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Actins / metabolism
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Alkyl and Aryl Transferases / antagonists & inhibitors
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Cell Adhesion / drug effects
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Cell Line
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Enzyme Activation
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Fatty Acids, Monounsaturated / pharmacology
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Fluvastatin
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Humans
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Indoles / pharmacology
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Intercellular Adhesion Molecule-1 / metabolism*
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Leucine / analogs & derivatives
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Leucine / pharmacology
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Phosphatidylcholines / metabolism*
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Phosphatidylcholines / pharmacology
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Protein Prenylation / drug effects
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RNA Interference
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rac GTP-Binding Proteins / antagonists & inhibitors
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rac GTP-Binding Proteins / genetics
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rac GTP-Binding Proteins / metabolism*
Substances
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Actins
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Fatty Acids, Monounsaturated
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GGTI 286
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Indoles
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Phosphatidylcholines
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phosphatidylcholine hydroperoxide
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Intercellular Adhesion Molecule-1
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Fluvastatin
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Alkyl and Aryl Transferases
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geranylgeranyltransferase type-I
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rac GTP-Binding Proteins
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Leucine