| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
Papers In Press, published online ahead of print April 1, 2005
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Cardiology Dept., Tulane University Health Sciences Center, New Orleans, LA 70112-2699
Corresponding Author: pdelafon{at}tulane.edu
Oxidized LDL (oxLDL) has multiple proatherogenic effects including induction of apoptosis. We have recently shown that oxLDL markedly downregulates insulin-like growth factor-1 (IGF-1) receptor in human aortic smooth muscle cells, and that IGF-1 receptor overexpression blocks oxLDL induced apoptosis. We hypothesized that specific oxLDL-triggered signaling events led to IGF-1 receptor downregulation and apoptosis. We examined oxLDL signaling pathways and found that neither IGF-1 receptor downregulation nor the pro-apoptotic effect were blocked by inhibition of oxLDL triggered ERK, p38 MAPK, or PPAR signaling pathways as assessed using specific inhibitors. However, antioxidants, PEG-catalase, superoxide dismutase and Trolox completely blocked oxLDL downregulation of IGF-1 receptor and oxLDL induced apoptosis. Nordihydroguaiaretic acid, AA-861 and baicalein,which are lipoxygenase inhibitors and also have antioxidant activity, blocked IGF-1 receptor downregulation and apoptosis as well as reactive oxygen species (ROS) production. These results suggest that oxLDL enhances ROS production possibly through lipoxygenase activity, leading to IGF-1 receptor downregulation and apoptosis. Furthermore, anti-CD36 scavenger receptor antibody markedly inhibited oxLDL induced IGF-1 receptor downregulation and apoptosis as well as ROS production. In conclusion, our data demonstrates that oxLDL downregulates IGF-1 receptor via redox-sensitive pathways that are distinct from oxLDL signaling through MAPK and PPAR involved pathways, however may involve CD36 dependent mechanism.
Revised on February 24, 2005
Accepted on March 21, 2005
A redox-sensitive pathway mediates oxidized LDL-induced downregulation ofInsulin-like growth factor-1 receptor
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  D. Allard, N. Figg, M. R. Bennett, and T. D. Littlewood Akt Regulates the Survival of Vascular Smooth Muscle Cells via Inhibition of FoxO3a and GSK3 J. Biol. Chem., July 11, 2008; 283(28): 19739 - 19747. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J.-S. Choi, Y.-J. Choi, S.-Y. Shin, J. Li, S.-W. Kang, J.-Y. Bae, D. S. Kim, G.-E. Ji, J.-S. Kang, and Y.-H. Kang Dietary Flavonoids Differentially Reduce Oxidized LDL-Induced Apoptosis in Human Endothelial Cells: Role of MAPK- and JAK/STAT-Signaling J. Nutr., June 1, 2008; 138(6): 983 - 990. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sukhanov, Y. Higashi, S.-Y. Shai, C. Vaughn, J. Mohler, Y. Li, Y.-H. Song, J. Titterington, and P. Delafontaine IGF-1 Reduces Inflammatory Responses, Suppresses Oxidative Stress, and Decreases Atherosclerosis Progression in ApoE-Deficient Mice Arterioscler. Thromb. Vasc. Biol., December 1, 2007; 27(12): 2684 - 2690. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Sukhanov, Y. Higashi, S.-Y. Shai, H. Itabe, K. Ono, S. Parthasarathy, and P. Delafontaine Novel Effect of Oxidized Low-Density Lipoprotein: Cellular ATP Depletion via Downregulation of Glyceraldehyde-3-Phosphate Dehydrogenase Circ. Res., July 21, 2006; 99(2): 191 - 200. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| All ASBMB Journals | Journal of Biological Chemistry |
| Molecular and Cellular Proteomics | ASBMB Today |
