Differential activation of heme oxygenase-1 by chalcones and rosolic acid in endothelial cells
Differential activation of heme oxygenase-1 by chalcones and rosolic acid in endothelial cells
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DOI：
10.1124/jpet.104.074153
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发表时间：
2005-02-01
影响因子：
3.5
通讯作者：
Motterlini, R
中科院分区：
文献类型：
--
作者：
Foresti, R;Hoque, M;Motterlini, R
血红素氧合酶-1（HO-1）的诱导被广泛认为是一种有效的细胞策略，以抵消各种应激事件。我们已经表明，姜黄素和咖啡酸苯乙酯，两种天然存在的植物化学物质，具有抗氧化，抗炎和抗癌活性，诱导HO-1在许多细胞类型。这表明HO-1的刺激可能部分地构成这些植物源成分所产生的有益作用的基础。在这里，我们研究了额外的植物成分的能力，以上调血红素加氧酶活性和HO-1在主动脉内皮细胞。内皮细胞与一系列多酚查耳酮（5 - 50 μ M）孵育导致血红素加氧酶活性增加;有趣的是，化学结构决定了血红素加氧酶诱导的模式，这对每种特定的化合物都是独特的。我们还发现从车前根茎中分离得到的成分玫瑰酸。以浓度和时间依赖性方式显著增加HO-1。在细胞长时间暴露于姜黄素和咖啡酸苯乙酯（24或48 h）后观察到严重的细胞毒性，而2 '-羟基查耳酮和玫瑰酸不影响细胞活力。通过使用不同的丝裂原活化蛋白激酶抑制剂，我们确定细胞外信号调节激酶，p38和c-Jun NH 2-末端蛋白激酶途径在玫瑰酸和2 '-羟基查耳酮诱导HO-1中仅起次要作用。另一方面，增加细胞内和细胞外硫醇显着降低玫瑰酸引起的血红素加氧酶活性的上升。因此，本研究鉴定了在内皮细胞中高度诱导HO-1的新植物成分，并研究了参与这种作用的一些机制。
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 muM) 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.