Prostaglandin D2 induces heme oxygenase-1 in human retinal pigment epithelial cells.
The retinal pigment epithelium (RPE) constitutes the blood-retinal barrier, whose function is impaired in various pathological conditions, including cerebral malaria, a lethal complication of Plasmodium falciparum infection. Prostaglandin (PG) D(2) is abundantly produced in the brain to regulate sleep responses. Moreover, PGD(2) is a potential factor derived from intra-erythrocyte falciparum parasites. Heme oxygenase-1 (HO-1) is important for iron homeostasis via catalysis of heme degradation to release iron, carbon monoxide and biliverdin/bilirubin, and may influence iron supply to the intra-erythrocyte falciparum parasites. Here, we showed that treatment of human RPE cell lines, ARPE-19 and D407, with PGD(2) significantly increased the expression levels of HO-1 mRNA, in a dose- and time-dependent manner. Transient expression assays showed that PGD(2) treatment increased the HO-1-gene promoter activity through the enhancer sequence, containing a Maf-recognition element. Thus, PGD(2) may contribute to the maintenance of heme homeostasis in the brain by inducing HO-1 expression.
Kuesap
Jiraporn
J
Department of Molecular Biology and Applied Physiology, Tohoku University School of Medicine, 2-1 Seiryo-machi, Aoba-ku, Sendai 980-8575, Japan.
Li
Bin
B
Satarug
Soisungwan
S
Takeda
Kazuhisa
K
Numata
Ikuko
I
Na-Bangchang
Kesara
K
Shibahara
Shigeki
S
D002460:Cell Line; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000201:enzymology*; D015230:Prostaglandin D2 / Q000008:administration & dosage*
C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; D015230:Prostaglandin D2