An involvement of SR-B1 mediated PI3K-Akt-eNOS signaling in HDL-induced cyclooxygenase 2 expression and prostacyclin production in endothelial cells

作者：Zhang, Qing-Hai; Zu, Xu-Yu; Cao, Ren-Xian; Liu, Jiang-Hua; Mo, Zhong-Cheng; Zeng, Ying; Li, Yuan-Bin; Xiong, Sheng-Lin; Liu, Xing; Liao, Duan-Fang; Yi, Guang-Hui^*

来源：Biochemical and Biophysical Research Communications, 2012, 420(1): 17-23.

DOI：10.1016/j.bbrc.2012.02.103

• HDL
• SR-B1
• PI3K
• eNOS
• COX-2
• PGI(2)

It is well-known that sphingosine-l-phosphate (SIP), the phospholipid content of HDL, binding to SIP receptors can raise COX-2 expression and PGI(2) release through p38MAPK/CREB pathway. In the present study we assess the action of SR-B1 initiated PI3K-Akt-eNOS signaling in the regulation of COX-2 expression and PGI(2) production in response to HDL. We found that apoA1 could increase PGI(2) release and COX-2 expression in ECV 304 endothelial cells. Furthermore, SR-B1 was found to be involved in HDL induced up-regulation of COX-2 and PGI(2). Over-expressed SR-B1 did not significantly increase the expression of COX-2 and the PGI(2) levels, but knock-down of SR-B1 by siRNA could significantly attenuate COX-2 expression and PGI(2) release together with p38MAPK and CREB phosphorylation. Consistently, the declines of p-p38MAPK, p-CREB, COX-2 and PGI(2) were also observed after incubation with LY294002 (25 mu mol/L; PI3K special inhibitor) or L-NAME (50 mu mol/L; eNOS special inhibitor). In addition, we demonstrated the increases of PGI(2) release, COX-2 expression and p38MAPK phosphorylation, when nitric oxide level was raised through the incubation of L-arginine (10 or 20 nmol/L) in endothelial cells. Taking together, our data support that SR-B1 mediated PI3K-Akt-eNOS signaling was involved in HDL-induced COX-2 expression and PGI(2) release in endothelial cells.

• 出版日期2012-3-30
• 单位湖南中医药大学; 南华大学