Premium
Role of LOX‐1 in monocyte adhesion‐triggered redox, Akt/eNOS and Ca 2+ signaling pathways in endothelial cells
Author(s) -
Sakamoto Nobuo,
Ishibashi Toshiyuki,
Sugimoto Koichi,
Sawamura Tatsuya,
Sakamoto Takayuki,
Inoue Nobutaka,
Saitoh Shuichi,
Kamioka Masashi,
Uekita Hironori,
Ohkawara Hiroshi,
Suzuki Koji,
Teramoto Tamio,
Maruyama Yukio,
Takeishi Yasuchika
Publication year - 2009
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.21818
Subject(s) - enos , protein kinase b , microbiology and biotechnology , chemistry , monocyte , cell adhesion , phosphorylation , signal transduction , nadph oxidase , biochemistry , reactive oxygen species , biology , immunology , nitric oxide synthase , cell , enzyme
This study was conducted to examine the role of lectin‐like oxidized low‐density lipoprotein receptor‐1 (LOX‐1) in monocyte adhesion‐induced redox‐sensitive, Akt/eNOS and Ca 2+ signaling pathways in endothelial cells (ECs). LOX‐1 was blocked by an antibody‐neutralizing LOX‐1 TS92 or small interfering RNA. In cultured human aortic ECs, monocyte adhesion activated Rac1 and p47 phox , and increased NADPH oxidase activity and reactive oxygen species (ROS) generation within 30 min and NF‐κB phosphorylation within 1 h, resulting in redox‐sensitive gene expression. Akt and eNOS phosphorylation was induced 15 min after adding monocytes and returned to control level after 30 min, whereas NO production was not altered by monocyte adhesion. Blockade of LOX‐1 blunted the monocyte adhesion‐triggered redox‐sensitive signaling pathway and Akt/eNOS phosphorylation in ECs. Both endothelial intracellular Ca 2+ mobilization and Ca 2+ influx caused by monocyte attachment were markedly attenuated by pretreatment of ECs with TS92. This suggests that LOX‐1 is involved in redox‐sensitive, Akt/eNOS and Ca 2+ signaling pathways in monocyte adhesion to ECs independent of oxidized low‐density lipoprotein (ox‐LDL). Furthermore, blockade of Ca 2+ inhibited monocyte adhesion‐triggered Rac1 and p47 phox activation and ROS generation in ECs, whereas Ca 2+ signaling was suppressed by blockade of NADPH oxidase and ROS generation. Finally, TS92 blocked the monocyte adhesion to ECs stimulated with or without tumor necrosis factor‐α or ox‐LDL. We provide evidence that LOX‐1 plays a role in redox‐sensitive, Akt/eNOS and Ca 2+ signaling pathways in monocyte adhesion to ECs independent of the ox‐LDL–LOX‐1 axis. J. Cell. Physiol. 220: 706–715, 2009. © 2009 Wiley‐Liss, Inc.