Protein Kinase C-eta and Phospholipase D2 Pathway Regulates Foam Cell Formation via Regulator of G Protein Signaling 2

Title
Protein Kinase C-eta and Phospholipase D2 Pathway Regulates Foam Cell Formation via Regulator of G Protein Signaling 2
Author(s)
백석환이형경여승은김진식이진구배외식[배외식]이추희
Keywords
FATTY-ACIDS PHOSPHORYLATE; BLOOD-PRESSURE; DESTABILIZE ABCA1; RGS PROTEINS; TNF-ALPHA; PKC-ETA; ACTIVATION; HYPERTENSION; MACROPHAGES; EXPRESSION
Issue Date
201006
Publisher
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
Citation
MOLECULAR PHARMACOLOGY, v.78, no.3, pp.478 - 485
Abstract
Regulator of G protein signaling 2 (RGS2) is a GTPase-activating protein for G alpha(q), which is involved in regulating various vascular functions. To understand how RGS2 regulates foam cell formation, the present study identified signaling pathways controlled by lipopolysaccharide (LPS) and discovered new mechanisms whereby protein kinase C (PKC)-eta and phospholipase D (PLD) 2 regulate RGS2 expression. The toll-like receptor (TLR) 4 agonist LPS caused foam cell formation of Raw264.7 macrophages and dramatically decreased RGS2 mRNA expression. RGS2 down-regulation by LPS was partially recovered by TLR4 small interfering RNA (siRNA). Peritoneal macrophages were separated from wild-type and TLR4 mutant mice, and treatment with LPS showed RGS2 expression decrease in wild-type macrophages but no change in TLR4 mutant macrophages. RGS2 overexpression was suppressed, whereas RGS2 down-regulation accelerated foam cell formation by LPS. Treatment of PKC-eta pseudosubstrate weakened foam cell formation and recovered RGS2 down-regulation by LPS. In addition, LPS or phorbol 12-myristate 13-acetate stimulated PLD activity, and the pretreatment of PLD inhibitor weakened foam cell formation and recovered RGS2 down-regulation. Inhibition of PLD2 expression by siRNA also weakened foam cell formation and partially recovered LPS-mediated RGS2 down-regulation. On the other hand, PLD2 overexpression intensified RGS2 down-regulation and foam cell formation by LPS. These results suggest that LPS causes foam cell formation by increasing PKC-eta and PLD2 activity by down-regulating RGS2 expression via TLR4 dependently.
URI
http://hdl.handle.net/YU.REPOSITORY/22385http://dx.doi.org/10.1124/mol.110.064394
ISSN
0026-895X
Appears in Collections:
의과대학 > 생화학.분자생물학교실 > Articles
의과대학 > 영상의학과학교실 > Articles
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