Hydroxytyrosol, a natural antioxidant from olive oil, prevents protein damage induced by long-wave ultraviolet radiation in melanoma cells
Hydroxytyrosol, a natural antioxidant from olive oil, prevents protein damage induced by long-wave ultraviolet radiation in melanoma cells
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DOI：
10.1016/j.freeradbiomed.2004.12.015
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发表时间：
2005-04-01
影响因子：
7.4
通讯作者：
Galletti, P
中科院分区：
文献类型：
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作者：
D'Angelo, S;Ingrosso, D;Galletti, P
以往的研究表明，长波紫外线（UVA）辐射通过产生活性氧和内源性抗氧化系统的耗竭引起严重的皮肤损伤。我们实验室最近的结果表明，在UVA照射的人黑色素瘤细胞中，脂质过氧化产物（TBARS）和异常的L-异戊酰残基（蛋白质损伤的标志物）急剧增加。在这项研究中，羟基酪醇（DOPET），在橄榄油中存在的主要抗氧化剂化合物，对UVA诱导的细胞损伤的影响，已被调查，使用人类黑色素瘤细胞系（M14）作为模型系统。在UVA照射的M14细胞中，观察到DOPET在防止氧化应激的典型标志物如TBARS和2 '7'-二氯荧光素（DCF）荧光强度升高方面的保护作用。此外，DOPET防止UVA照射诱导的改变的L-isoAsp残基的增加。这些保护作用是剂量依赖性的，在400 μ M DOPET时达到最大。在较高浓度下，DOPET引起M14细胞增殖停滞，并通过激活半胱天冬酶-3活性作为促凋亡刺激物。在所研究的模型系统中，DOPET被定量地转化成其甲基化衍生物，赋予与其母体化合物相当的自由基清除能力。这些发现与氧化应激在介导UVA诱导的蛋白质损伤中起主要作用的假设一致。结果表明，DOPET可能会根据所用剂量对黑色素瘤细胞产生不同的影响，当使用橄榄油衍生的大型消费品（包括化妆品和功能性食品）时，必须始终考虑到这一点。(c)2004爱思唯尔公司All rights reserved.
Previous studies showed that long-wave ultraviolet (UVA) radiation induces severe skin damage through the generation of reactive oxygen species and the depletion of endogenous antioxidant systems. Recent results from our laboratory indicate a dramatic increase of both lipid peroxidation products (TBARS) and abnormal L-isoaspartyl residues, marker of protein damage, in UVA-irradiated human melanoma cells. In this study, the effects of hydroxytyrosol (DOPET), the major antioxidant compound present in olive oil, on UVA-induced cell damages, have been investigated, using a human melanoma cell line (M14) as a model system. In UVA-irradiated M14 cells, a protective effect of DOPET in preventing the uprise of typical markers of oxidative stress, such as TBARS and 2'7'-dichlorofluorescein (DCF) fluorescence intensity, was observed. In addition, DOPET prevents the increase of altered L-isoAsp residues induced by UVA irradiation. These protective effects are dose dependent, reaching the maximum at 400 mu M DOPET. At higher concentrations, DOPET causes an arrest of M14 cell proliferation and acts as a proapoptotic stimulus by activating caspase-3 activity. In the investigated model system, DOPET is quantitatively converted into its methylated derivative, endowed with a radical scavenging ability comparable to that of its parent compound. These findings are in line with the hypothesis that the oxidative stress plays a major role in mediating the UVA-induced protein damage. Results suggest that DOPET may exerts differential effects on melanoma cells according to the dose employed and this must always be taken into account when olive oil-derived large consumer products, including cosmetics and functional foods, are employed. (c) 2004 Elsevier Inc. All rights reserved.