| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Journal of Lipid Research, Vol 36, 2005-2016, Copyright © 1995 by Lipid Research, Inc.
V Natarajan, WM Scribner, CM Hart and S Parthasarathy
Low density lipoproteins (LDL) are risk factors in atherosclerosis and
oxidative modification of LDL to oxidized LDL (OX-LDL) increases its
atherogenicity. Development of atherosclerosis likely involves OX-LDL-
mediated smooth muscle cell (SMC) proliferation. However, the mechanism(s)
of SMC proliferation by OX-LDL is unknown. We hypothesized that OX-LDL may
mediate SMC proliferation by activation of phospholipase D (PLD) through
the generation of the second-messenger, phosphatidic acid (PA). To test
this hypothesis, activation of PLD by OX-LDL was investigated in
[3H]myristic acid- or [32P]orthophosphate- labeled rabbit femoral artery
smooth muscle cells (RFASMC) in the presence of 0.5% ethanol or 0.05%
butanol. Phospholipase D activation, as measured by labeled
phosphatidylethanol (PEt) or phosphatidylbutanol (PBt) formation, was
enhanced (3- to 5-fold) by OX-LDL. This activation of PLD was specific for
OX-LDL, as native LDL or acetylated LDL had no effect. Further,
OX-LDL-mediated [32P]PEt formation was dose- and time- dependent. To
determine the mechanism(s) of OX-LDL-induced PLD activation, the role of
protein kinase C (PKC) and Ca2+ was investigated. Pretreatment of
[32P]orthophosphate-labeled RFASMC with known inhibitors of PKC such as
staurosporine, calphostin-C, or H-7, had no effect on OX-LDL-induced PLD
activation. Also, down-regulation of PKC by 12-O-tetradecanoylphorbol
13-acetate (TPA) (100 nM, 18 h) did not alter the OX-LDL-mediated [32P]PEt
formation. However, pretreatment of RFASMC with genistein, a putative
inhibitor of tyrosine kinases, attenuated the OX-LDL-mediated [32P]PEt
formation. In addition, exposure of RFASMC to sodium orthovanadate, an
inhibitor of phosphatases, enhanced the OX-LDL-mediated PLD activation. The
effects of genistein and vanadate on PLD activation were specific for
OX-LDL as these agents did not alter the TPA-induced [32P]PEt formation.
Treatment of quiescent RFASMC with OX-LDL increased [3H]thymidine
incorporation into DNA. This enhanced incorporation of [3H]thymidine into
DNA was also mimicked by exogenously added phosphatidic acid (PA) or
lysophosphatidic acid (LPA). These findings suggest that OX-LDL is a potent
activator of the PLD pathway in SMC. The activation of PLD by OX- LDL
generates second-messengers like PA and/or LPA which modulate mitogenesis.
Thus, these results indicate that OX-LDL, in atherosclerotic lesions, may
enhance SMC proliferation through the modulation of signal transduction
pathways including activation of PLD.
ARTICLES
Oxidized low density lipoprotein-mediated activation of phospholipase D in smooth muscle cells: a possible role in cell proliferation and atherogenesis
Department of Medicine, Indiana University School of Medicine, Indianapolis, USA.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  K. Kotarsky, A. Boketoft, J. Bristulf, N. E. Nilsson, A. Norberg, S. Hansson, C. Owman, R. Sillard, L. M. F. Leeb-Lundberg, and B. Olde Lysophosphatidic Acid Binds to and Activates GPR92, a G Protein-Coupled Receptor Highly Expressed in Gastrointestinal Lymphocytes J. Pharmacol. Exp. Ther., August 1, 2006; 318(2): 619 - 628. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Kawakami, A. Tanaka, T. Chiba, K. Nakajima, K. Shimokado, and M. Yoshida Remnant Lipoprotein-Induced Smooth Muscle Cell Proliferation Involves Epidermal Growth Factor Receptor Transactivation Circulation, November 25, 2003; 108(21): 2679 - 2688. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Wang, R. Cummings, Y. Zhao, A. Kazlauskas, J. K. S. Sham, A. Morris, S. Georas, D. N. Brindley, and V. Natarajan Involvement of Phospholipase D2 in Lysophosphatidate-induced Transactivation of Platelet-derived Growth Factor Receptor-{beta} in Human Bronchial Epithelial Cells J. Biol. Chem., October 10, 2003; 278(41): 39931 - 39940. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M.-W. Chien, C.-S. Chien, L.-D. Hsiao, C.-H. Lin, and C.-M. Yang OxLDL induces mitogen-activated protein kinase activation mediated via PI3-kinase/Akt in vascular smooth muscle cells J. Lipid Res., September 1, 2003; 44(9): 1667 - 1675. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Salh, K. Assi, S. Huang, L. O'Brien, U. Steinbrecher, and A. Gomez-Munoz Dissociated ROS production and ceramide generation in sulfasalazine-induced cell death in Raw 264.7 cells J. Leukoc. Biol., October 1, 2002; 72(4): 790 - 799. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. GOUNI-BERTHOLD and A. SACHINIDIS Does the coronary risk factor low density lipoprotein alter growth and signaling in vascular smooth muscle cells? FASEB J, October 1, 2002; 16(12): 1477 - 1487. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Perez-Andres, M. Fernandez-Rodriguez, M. Gonzalez, A. Zubiaga, A. Vallejo, I. Garcia, C. Matute, S. Pochet, J. P. Dehaye, M. Trueba, et al. Activation of phospholipase D-2 by P2X7 agonists in rat submandibular gland acini J. Lipid Res., August 1, 2002; 43(8): 1244 - 1255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Escargueil-Blanc, R. Salvayre, N. Vacaresse, G. Jurgens, B. Darblade, J.-F. Arnal, S. Parthasarathy, and A. Negre-Salvayre Mildly Oxidized LDL Induces Activation of Platelet-Derived Growth Factor {beta}-Receptor Pathway Circulation, October 9, 2001; 104(15): 1814 - 1821. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Natarajan, W. M. Scribner, A. J. Morris, S. Roy, S. Vepa, J. Yang, R. Wadgaonkar, S. P. M. Reddy, J. G. N. Garcia, and N. L. Parinandi Role of p38 MAP kinase in diperoxovanadate-induced phospholipase D activation in endothelial cells Am J Physiol Lung Cell Mol Physiol, August 1, 2001; 281(2): L435 - L449. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yasunari, K. Maeda, M. Minami, and J. Yoshikawa HMG-CoA Reductase Inhibitors Prevent Migration of Human Coronary Smooth Muscle Cells Through Suppression of Increase in Oxidative Stress Arterioscler. Thromb. Vasc. Biol., June 1, 2001; 21(6): 937 - 942. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Kataoka, N. Kume, S. Miyamoto, M. Minami, M. Morimoto, K. Hayashida, N. Hashimoto, and T. Kita Oxidized LDL Modulates Bax/Bcl-2 Through the Lectinlike Ox-LDL Receptor-1 in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., June 1, 2001; 21(6): 955 - 960. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gomez-Munoz, J. S. Martens, and U. P. Steinbrecher Stimulation of Phospholipase D Activity by Oxidized LDL in Mouse Peritoneal Macrophages Arterioscler. Thromb. Vasc. Biol., January 1, 2000; 20(1): 135 - 143. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Vepa, W. M. Scribner, N. L. Parinandi, D. English, J. G. N. Garcia, and V. Natarajan Hydrogen peroxide stimulates tyrosine phosphorylation of focal adhesion kinase in vascular endothelial cells Am J Physiol Lung Cell Mol Physiol, July 1, 1999; 277(1): L150 - L158. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Gómez-Muñoz, L. O'Brien, R. Hundal, and U. P. Steinbrecher Lysophosphatidylcholine stimulates phospholipase D activity in mouse peritoneal macrophages J. Lipid Res., June 1, 1999; 40(6): 988 - 993. [Abstract] [Full Text]
|
|
|
|
|
|
I. Suc, O. Meilhac, I. Lajoie-mazenc, J. Vandaele, G. Jürgens, R. Salvayre, and A. Nègre-salvayre Activation of EGF receptor by oxidized LDL FASEB J, June 1, 1998; 12(9): 665 - 671. [Abstract] [Full Text]
|
|
|
|
|
|
J. Ruef, G. N. Rao, F. Li, C. Bode, C. Patterson, A. Bhatnagar, and M. S. Runge Induction of Rat Aortic Smooth Muscle Cell Growth by the Lipid Peroxidation Product 4-Hydroxy-2-Nonenal Circulation, March 24, 1998; 97(11): 1071 - 1078. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. S. Martens, N. E. Reiner, P. Herrera-Velit, and U. P. Steinbrecher Phosphatidylinositol 3-Kinase Is Involved in the Induction of Macrophage Growth by Oxidized Low Density Lipoprotein J. Biol. Chem., February 27, 1998; 273(9): 4915 - 4920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. Cox and M. L. Cohen Relationship between Phospholipase D Activation and Endothelial Vasomotor Dysfunction in Rabbit Aorta J. Pharmacol. Exp. Ther., October 1, 1997; 283(1): 305 - 311. [Abstract] [Full Text]
|
|
|
|
|
|
D. P. Hajjar and M. E. Haberland Lipoprotein Trafficking in Vascular Cells. MOLECULAR TROJAN HORSES AND CELLULAR SABOTEURS J. Biol. Chem., September 12, 1997; 272(37): 22975 - 22978. [Full Text] [PDF]
|
|
|
|
|
|
N. Auge, N. Andrieu, A. Negre-Salvayre, J.-C. Thiers, T. Levade, and R. Salvayre The Sphingomyelin-Ceramide Signaling Pathway Is Involved in Oxidized Low Density Lipoprotein-induced Cell Proliferation J. Biol. Chem., August 9, 1996; 271(32): 19251 - 19255. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Scheidegger, R. W. James, and P. Delafontaine Differential Effects of Low Density Lipoproteins on Insulin-like Growth Factor-1 (IGF-1) and IGF-1 Receptor Expression in Vascular Smooth Muscle Cells J. Biol. Chem., August 25, 2000; 275(35): 26864 - 26869. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Zhao, J. Letterman, and B. M. Schreiber beta -Migrating Very Low Density Lipoprotein (beta VLDL) Activates Smooth Muscle Cell Mitogen-activated Protein (MAP) Kinase via G Protein-coupled Receptor-mediated Transactivation of the Epidermal Growth Factor (EGF) Receptor. EFFECT OF MAP KINASE ACTIVATION ON beta VLDL PLUS EGF-INDUCED CELL PROLIFERATION J. Biol. Chem., August 10, 2001; 276(33): 30579 - 30588. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
