on March 15, 2007
Published online before print March 15, 2007, doi: 10.1161/ATVBAHA.106.132837
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on September 26, 2006
Accepted on February 14, 2007
Acrolein Induces Cyclooxygenase-2 and Prostaglandin Production in Human Umbilical Vein Endothelial Cells. Roles of p38 MAP Kinase
Yong Seek Park ;
From the Department of Biochemistry (Y.S.P., Y.M., R.T., M.T., N.T.) and the Department of Disease Glycomics, Research Institute for Microbial Diseases (N.T.), Osaka University, Japan; the Department of Microbiology (Y.S.P.), College of Medicine, Kyung Hee University, Seoul, Korea; and the Urological Diseases Research Center (J.K., M.R.F.), Children’s Hospital Boston, Harvard Medical School, Boston, Mass.
* To whom correspondence should be addressed. E-mail: tani52{at}wd5.so-net.ne.jp.
Objective--Acrolein, a known toxin in tobacco smoke, might be involved in atherogenesis. This study examined the effect of acrolein on expression of cyclooxygenase-2(COX-2) and prostaglandin (PG) production in endothelial cells.
Methods and Results--Cyclooxygenase (COX)-2 induction by acrolein and signal pathways were measured using Western blots, Northern blots, immunoflouresence, ELISA, gene silencing, and promoter assay. Colocalization of COX2 and acrolein-adduct was determined by immunohistochemistry. Here we report that the levels of COX-2 mRNA and protein are increased in human umbilical vein endothelial cells (HUVECs) after acrolein exposure. COX-2 was found to colocalize with acrolein-lysine adducts in human atherosclerotic lesions. Inhibition of p38 MAPK activity abolished the induction of COX-2 protein and PGE2 accumulation by acrolein, while suppression of extracellular signal-regulated kinase (ERK) and JNK activity had no effect on the induction of COX-2 expression in experiments using inhibitors and siRNA. Furthermore, rottlerin, an inhibitor of protein kinase C
(PKC), abrogated the upregulation of COX-2 at both protein and mRNA levels.
Conclusion--These results provide that acrolein may play a role in progression of atherosclerosis and new information on the signaling pathways involved in COX-2 upregulation in response to acrolein and provide evidence that PKC and p38 MAPK are required for transcriptional activation of COX-2.
Key words: acrolein • COX-2 • p38 MAPK • atherosclerosis • endothelial cells
This article has been cited by other articles:
 |
|
 |
|
  C.-M. Yang, I-T. Lee, C.-C. Lin, Y.-L. Yang, S.-F. Luo, Y. R. Kou, and L.-D. Hsiao Cigarette smoke extract induces COX-2 expression via a PKC{alpha}/c-Src/EGFR, PDGFR/PI3K/Akt/NF-{kappa}B pathway and p300 in tracheal smooth muscle cells Am J Physiol Lung Cell Mol Physiol, November 1, 2009; 297(5): L892 - L902. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Wang, Y. Liu, L. Chen, X. Wang, X-R. Hu, Y-L. Feng, D-S. Liu, D. Xu, Y-P. Duan, J. Lin, et al. Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats Eur. Respir. J., May 1, 2009; 33(5): 1122 - 1132. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Yamawaki, K. Saito, M. Okada, and Y. Hara Methylglyoxal mediates vascular inflammation via JNK and p38 in human endothelial cells Am J Physiol Cell Physiol, December 1, 2008; 295(6): C1510 - C1517. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. D. Lamon and D. P. Hajjar Inflammation at the Molecular Interface of Atherogenesis: An Anthropological Journey Am. J. Pathol., November 1, 2008; 173(5): 1253 - 1264. [Abstract] [Full Text] [PDF]
|
|