Concurrent expression of heme oxygenase-1 and p53 in human retinal pigment epithelial cell line.
Heme oxygenase-1 (HO-1) is a stress-responsive protein that is known to regulate cellular functions such as cell proliferation, inflammation, and apoptosis. Here, we investigated the effects of HO activity on the expression of p53 in the human retinal pigment epithelium (RPE) cell line ARPE-19. Cobalt protoporphyrin (CoPP) induced the expression of both HO-1 and p53 without significant toxicity to the cells. In addition, the blockage of HO activity with the iron chelator DFO or with HO-1 siRNA inhibited the CoPP-induced expression of p53. Similarly, zinc protoporphyrin (ZnPP), an inhibitor of HO, suppressed p53 expression in ARPE-19 cells, although ZnPP increased the level of HO-1 protein while inhibiting HO activity. Also, CoPP-induced p53 expression was not affected by the formation of reactive oxygen species (ROS). Based on these results, we conclude that HO activity is involved in the regulation of p53 expression in a ROS-independent mechanism, and also suggest that the expression of p53 in ARPE-19 cells is associated with heme metabolites such as biliverdin/bilirubin, carbon monoxide, and iron produced by the activity of HO.
Department of Biochemistry, Pusan National University School of Medicine, Busan 602-739, Republic of Korea.
Sang Yull
SY
Lee
Hong Jae
HJ
Jo
Kang Mi
KM
Kim
Ju Dong
JD
Song
Hun Taeg
HT
Chung
Young Chul
YC
Park
D002460:Cell Line; D005786:Gene Expression Regulation / Q000502:physiology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D006801:Humans; D010857:Pigment Epithelium of Eye / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*
C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051547:Heme Oxygenase-1