TY - JOUR
T1 - Prostaglandin D2 induces heme oxygenase-1 mRNA expression through the DP2 receptor
AU - Satarug, Soisungwan
AU - Wisedpanichkij, Raewadee
AU - Takeda, Kazuhisa
AU - Li, Bin
AU - Na-Bangchang, Kesara
AU - Moore, Michael R.
AU - Shibahara, Shigeki
N1 - Funding Information:
This work was supported in part by Grant-in-Aid for Scientific Research on Priority Areas, and the 21st Century COE Program Special Research Grant “the Center for Innovative Therapeutic Development for Common Diseases” from the Ministry of Education, Science, Sports, and Culture of Japan. S. Satarug (ID NO. L 07568) was supported by the Research Fellowship (long-term) from Japan Society for the Promotion of Science (JSPS).
PY - 2008/12/19
Y1 - 2008/12/19
N2 - Prostaglandin (PG) D2 exerts multiple actions through interaction with distinct receptors, DP1 and DP2. We have shown that PGD2 induces the expression of heme oxygenase-1 (HO-1) in the retinal pigment epithelium (RPE) that is essential for survival of photoreceptors. HO-1 is a key enzyme in physiological heme degradation. Here, we explored the mechanism for the PGD2-mediated induction of HO-1 expression using ARPE-19 human RPE cells. ARPE-19 cells secrete PGD2 and express DP2 mRNA, but not DP1 mRNA. Treatment with a DP2 agonist, 15(R)-15-methyl-PGD2 or DK-PGD2, increased HO-1 mRNA expression, and pretreatment with a DP2 antagonist, CAY10471, decreased the magnitude of the PGD2-mediated HO-1 induction. By contrast, either DP1 agonist or antagonist caused only marginal influence on HO-1 expression. Moreover, transient expression assays showed the DP2 agonist activated the HO-1-gene promoter in the enhancer-dependent manner. Thus, PGD2 induces HO-1 mRNA expression through DP2 receptor, linking the PGD2-DP2 signaling with heme homeostasis.
AB - Prostaglandin (PG) D2 exerts multiple actions through interaction with distinct receptors, DP1 and DP2. We have shown that PGD2 induces the expression of heme oxygenase-1 (HO-1) in the retinal pigment epithelium (RPE) that is essential for survival of photoreceptors. HO-1 is a key enzyme in physiological heme degradation. Here, we explored the mechanism for the PGD2-mediated induction of HO-1 expression using ARPE-19 human RPE cells. ARPE-19 cells secrete PGD2 and express DP2 mRNA, but not DP1 mRNA. Treatment with a DP2 agonist, 15(R)-15-methyl-PGD2 or DK-PGD2, increased HO-1 mRNA expression, and pretreatment with a DP2 antagonist, CAY10471, decreased the magnitude of the PGD2-mediated HO-1 induction. By contrast, either DP1 agonist or antagonist caused only marginal influence on HO-1 expression. Moreover, transient expression assays showed the DP2 agonist activated the HO-1-gene promoter in the enhancer-dependent manner. Thus, PGD2 induces HO-1 mRNA expression through DP2 receptor, linking the PGD2-DP2 signaling with heme homeostasis.
KW - Cadmium
KW - DP2 receptor
KW - Heme oxygenase
KW - Macular degeneration
KW - Malaria
KW - Prostaglandin D
KW - Retina
KW - Stress
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UR - http://www.scopus.com/inward/citedby.url?scp=56049119088&partnerID=8YFLogxK
U2 - 10.1016/j.bbrc.2008.10.094
DO - 10.1016/j.bbrc.2008.10.094
M3 - Article
C2 - 18957281
AN - SCOPUS:56049119088
SN - 0006-291X
VL - 377
SP - 878
EP - 883
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
IS - 3
ER -
