© 2003 by European Society of Cardiology
Copyright © 2003, European Society of Cardiology
PKC/Raf/MEK/ERK signaling pathway modulates native-LDL-induced E2F-1 gene expression and endothelial cell proliferation
aDepartment of Biomedical Sciences, Division of Biochemistry, Laboratory of Cardiovascular Research, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
bDivision of Cell Biology, National Institute of Biostructures and Biosystems, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
cInstitute of Clinical Biochemistry, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy
gpintus{at}uniss.it
gionfry_p{at}yahoo.it
* Corresponding author. Department of Biomedical Sciences, Division of Biochemistry, Laboratory of Cardiovascular Research, University of Sassari, Viale San Pietro 43/B, 07100 Sassari, Italy. Tel.: +39-079-228-121; fax: +39-079-228-120.
Background and objectives: The interactions of low-density lipoprotein (LDL) with the endothelium are thought to play a major role in the development of atherosclerosis. Due to this reason, the molecular sequelae of events resulting from native LDL (N-LDL) interaction with human endothelial cells (HECs) are largely under investigation. Methods and results: Here, we report that the exposure of serum-free HECs to different concentrations of N-LDL-cholesterol (LDL-chol) elicited a time- and dose-dependent induction of DNA synthesis. The exposure of serum-free HECs to N-LDL was able to elicit a time- and dose-dependent increase of protein kinase C (PKC) activity that, along with the activation of the Raf/mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway, leads to an increase in E2F-1 gene expression. In addition, the treatment of HECs with N-LDL was also able to induce both E2F-1 gene transcription and protein expression. These N-LDL-aroused responses were dramatically counteracted by PKC inhibition or down regulation. Similarly to what observed for Raf/MEK/ERK activation and E2F-1 gene expression, the inhibition of PKC as well as its down regulation, significantly lowered the DNA synthesis induced by N-LDL in serum-free HECs. Conclusions: These results suggest that the activation of PKC/Raf/MEK/ERK-mediated events controlling E2F-1 gene expression by N-LDL may represent an important mechanism in the regulation of HECs proliferation during normal and pathological processes.
KEYWORDS Endothelial function; Gene expression; Lipoproteins; Protein kinases; Signal transduction
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  S. Wang, Z. Gong, R. Chen, Y. Liu, A. Li, G. Li, and J. Zhou JWA regulates XRCC1 and functions as a novel base excision repair protein in oxidative-stress-induced DNA single-strand breaks Nucleic Acids Res., April 1, 2009; 37(6): 1936 - 1950. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Kashima, T. Shiozawa, T. Miyamoto, A. Suzuki, J. Uchikawa, M. Kurai, and I. Konishi Autocrine stimulation of IGF1 in estrogen-induced growth of endometrial carcinoma cells: involvement of the mitogen-activated protein kinase pathway followed by up-regulation of cyclin D1 and cyclin E Endocr. Relat. Cancer, March 1, 2009; 16(1): 113 - 122. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Liao, Y. Zhang, and M. L. Dufau Protein Kinase C{alpha}-Induced Derepression of the Human Luteinizing Hormone Receptor Gene Transcription through ERK-Mediated Release of HDAC1/Sin3A Repressor Complex from Sp1 Sites Mol. Endocrinol., June 1, 2008; 22(6): 1449 - 1463. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. O. Apostolov, A. G. Basnakian, X. Yin, E. Ok, and S. V. Shah Modified LDLs induce proliferation-mediated death of human vascular endothelial cells through MAPK pathway Am J Physiol Heart Circ Physiol, April 1, 2007; 292(4): H1836 - H1846. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Cuschieri, J. Billgren, and R. V. Maier Phosphatidylcholine-specific phospholipase C (PC-PLC) is required for LPS-mediated macrophage activation through CD14 J. Leukoc. Biol., August 1, 2006; 80(2): 407 - 414. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Rucci, C. DiGiacinto, L. Orru, D. Millimaggi, R. Baron, and A. Teti A novel protein kinase C {alpha}-dependent signal to ERK1/2 activated by {alpha}V{beta}3 integrin in osteoclasts and in Chinese hamster ovary (CHO) cells J. Cell Sci., August 1, 2005; 118(15): 3263 - 3275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Crespo, J. Martinez-Gonzalez, J. Rius, and L. Badimon Simvastatin inhibits NOR-1 expression induced by hyperlipemia by interfering with CREB activation Cardiovasc Res, August 1, 2005; 67(2): 333 - 341. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Rius, J. Martinez-Gonzalez, J. Crespo, and L. Badimon Involvement of Neuron-Derived Orphan Receptor-1 (NOR-1) in LDL-Induced Mitogenic Stimulus in Vascular Smooth Muscle Cells: Role of CREB Arterioscler Thromb Vasc Biol, April 1, 2004; 24(4): 697 - 702. [Abstract] [Full Text] [PDF]
|
|