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Effects of Cyclopentenone Prostaglandins on the Expression of Heme Oxygenase‐1 in MCF‐7 Cells
Author(s) -
KIM EUNHEE,
KIM DOHEE,
NA HYEKYUNG,
SURH YOUNGJOON
Publication year - 2004
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1329.061
Subject(s) - heme oxygenase , cyclopentenone , protein kinase b , heme , chemistry , phosphorylation , biliverdin , biochemistry , kinase , pi3k/akt/mtor pathway , enzyme , signal transduction , stereochemistry
A bstract : Cyclopentenone prostaglandins (cyPGs) are produced by dehydration of precursor molecules. The cyPGs are reported to have proapoptotic effects in a variety of cell types. However, cyPGs, particularly 15‐deoxy‐Δ 12,14 ‐prostaglandin J 2 (15d‐PGJ 2 ), can also exert cytoprotective effects at relatively low concentrations. The cytoprotective activity of cyPGs appears to be mediated by the reactive α,β‐unsaturated carbonyl group located in the cyclopentene ring. In this study, we investigated the effect of cyPGs on the expression of heme oxygenase‐1 (HO‐1), a ubiquitous stress‐responsive enzyme that catalyzes oxidative cleavage of heme to form iron, carbon monoxide, and biliverdin. Treatment of the human breast cancer cell line (MCF‐7) with 15d‐PGJ 2 resulted in a concentration‐ and time‐dependent increase in the expression of HO‐1, whereas prostaglandin A 2 (PGA 2 ) and the non‐PG derivative 2‐cyclopenten‐1‐one failed to induce HO‐1 expression at the protein level. RT‐PCR revealed that the expression of HO‐1 mRNA was induced at 6 h by 15d‐PGJ 2 at 10 μM. However, PGA 2 induced HO‐1 mRNA expression at a higher concentration (30 μM). 2‐Cyclopenten‐1‐one did not induce the expression of HO‐1 mRNA at all. Likewise, 15d‐PGJ 2 treatment for 6 h led to phosphorylation of Akt/protein kinase B (PKB) to a greater extent than that achieved with PGA 2 . Thus, the induction of HO‐1 expression and the activation of Akt/PKB by 15d‐PGJ 2 and PGA 2 are likely to confer cytoprotective or antiapoptotic effects exerted by these cyPGs.