Differential Activation of Heme Oxygenase-1 by Chalcones and Rosolic Acid in Endothelial Cells
- 10 November 2004
- journal article
- Published by American Society for Pharmacology & Experimental Therapeutics (ASPET) in Journal of Pharmacology and Experimental Therapeutics
- Vol. 312 (2), 686-693
- https://doi.org/10.1124/jpet.104.074153
Abstract
The induction of heme oxygenase-1 (HO-1) is widely recognized as an effective cellular strategy to counteract a variety of stressful events. We have shown that curcumin and caffeic acid phenethyl ester, two naturally occurring phytochemicals that possess antioxidant, anti-inflammatory, and anticarcinogenic activities, induce HO-1 in many cell types. This suggests that stimulation of HO-1 could partly underlie the beneficial effects exerted by these plant-derived constituents. Here we examined the ability of additional plant constituents to up-regulate heme oxygenase activity and HO-1 in aortic endothelial cells. Incubation of endothelial cells with a series of polyphenolic chalcones (5–50 μM) resulted in increased heme oxygenase activity; interestingly, the chemical structure dictated the pattern of heme oxygenase induction, which was unique to each particular compound employed. We also found that rosolic acid, a constituent isolated from the rhizome of Plantago asiatica L. dramatically increased HO-1 in a concentration- and time-dependent manner. Severe cytotoxicity was observed after prolonged exposure (24 or 48 h) of cells to curcumin and caffeic acid phenethyl ester, whereas 2′-hydroxychalcone and rosolic acid did not affect cell viability. By using different mitogen-activated protein kinase inhibitors, we determined that the extracellular signal-regulated kinase, p38, and c-Jun NH2-terminal protein kinase pathways play only a minor role in the induction of HO-1 by rosolic acid and 2′-hydroxychalcone. On the other hand, increased intra- and extracellular thiols markedly reduced the rise in heme oxygenase activity elicited by rosolic acid. Thus, this study identified novel plant constituents that highly induce HO-1 in endothelial cells and investigated some of the mechanisms involved in this effect.Keywords
This publication has 34 references indexed in Scilit:
- Role of nuclear factor‐κB and heme oxygenase‐1 in the mechanism of action of an anti‐inflammatory chalcone derivative in RAW 264.7 cellsBritish Journal of Pharmacology, 2004
- Anti-Inflammatory Compounds of Plant Origin. Part I. Action on Arachidonic Acid Pathway, Nitric Oxide and Nuclear Factor κ B (NF-κB)Planta Medica, 2003
- Cardioprotective Actions by a Water-Soluble Carbon Monoxide–Releasing MoleculeCirculation Research, 2003
- Curcumin activates the haem oxygenase-1 gene via regulation of Nrf2 and the antioxidant-responsive elementBiochemical Journal, 2003
- Regulation of Heme Oxygenase-1 by Redox Signals Involving Nitric OxideAntioxidants and Redox Signaling, 2002
- Heme Oxygenase-1American Journal of Respiratory Cell and Molecular Biology, 2002
- Emerging Role of Carbon Monoxide in Physiologic and Pathophysiologic StatesAntioxidants and Redox Signaling, 2002
- THE HEME OXYGENASE SYSTEM:A Regulator of Second Messenger GasesAnnual Review of Pharmacology and Toxicology, 1997
- Heme oxygenase-1: function, regulation, and implication of a novel stress-inducible protein in oxidant-induced lung injury.American Journal of Respiratory Cell and Molecular Biology, 1996
- Transfection of the human heme oxygenase gene into rabbit coronary microvessel endothelial cells: protective effect against heme and hemoglobin toxicity.Proceedings of the National Academy of Sciences, 1995