15d-PGJ2 stimulates HO-1 expression through p38 MAP kinase and Nrf-2 pathway in rat vascular smooth muscle cells.
15d-PGJ(2), a potent endogenous ligand for peroxisome proliferators activated receptor-gamma, is a cyclopentenone-type prostaglandin produced by many different types of cells. Pertinent to its effect on vascular smooth muscle cell (VSMC), antiproliferative effects have been most frequently reported. In the present study, we investigated the effect of 15d-PGJ(2) on HO-1 expression that has been reported to inhibit VSMC proliferation. According to our data, 15d-PGJ(2) significantly induced ROS/NO production and HO-1 expression in rVSMCs. We also observed 15d-PGJ(2)-induced translocation of Nrf-2. In addition, ROS scavenger pretreatment suppressed 15d-PGJ(2)-induced HO-1 expression while PPARgamma antagonist did not, suggesting nuclear translocation of Nrf-2 and subsequent HO-1 expression was ROS dependent rather than PPARgamma dependent. Furthermore, an inhibitor of p38 MAPK abolished 15d-PGJ(2)-induced HO-1 expression. These data suggest that 15d-PGJ(2)-induced up-regulation of HO-1 is independent of PPARgamma but dependent of ROS and p38 MAPK pathway. The present study reports for the first time that 15d-PGJ(2) induces HO-1 expression possibly using Nrf-2 pathway as a response to ROS in VSMCs.
Lim
Hyun-Joung
HJ
Division of Cardiovascular Diseases, Center for Biomedical Sciences, National Institute of Health, Seoul, Republic of Korea.
Lee
Kuy-Sook
KS
Lee
Seahyoung
S
Park
Jin-Hee
JH
Choi
Hye-Eun
HE
Go
Sang Hee
SH
Kwak
Hyun-Jeong
HJ
Park
Hyun-Young
HY
D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004336:Drug Antagonism; D004338:Drug Combinations; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000096:biosynthesis*; D009569:Nitric Oxide / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
C477819:15-deoxyprostaglandin J2; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D016166:Free Radical Scavengers; D051267:NF-E2-Related Factor 2; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D051547:Heme Oxygenase-1; D048051:p38 Mitogen-Activated Protein Kinases; D015230:Prostaglandin D2