17β-oestradiol up-regulates longevity-related, antioxidant enzyme expression via the ERK1 and ERK2[MAPK]/NFκB cascade
17β-oestradiol up-regulates longevity-related, antioxidant enzyme expression via the ERK1 and ERK2[MAPK]/NFκB cascade
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DOI：
10.1111/j.1474-9726.2005.00151.x
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发表时间：
2005-06-01
期刊：
影响因子：
7.8
通讯作者：
Viña, J
中科院分区：
文献类型：
--
作者：
Borrás, C;Gambini, J;Viña, J
女性比男性寿命更长。雌激素通过上调抗氧化剂、长寿相关基因（如谷胱甘肽过氧化物酶 (GPx) 和锰超氧化物歧化酶 (Mn-SOD)）的表达来保护女性免受衰老。雌激素上调这些酶的机制仍不清楚，但可能对寿命的性别差异产生影响。我们发现，生理浓度的雌二醇通过雌激素受体发挥作用，降低 MCF-7 细胞（乳腺肿瘤细胞系）中的过氧化物水平。 MCF-7 细胞中 ERK1 和 ERK2 磷酸化表明雌二醇可增加 MAP 激酶 (MAPK) 激活，进而激活核因子 kappa B (NF kappa B) 信号通路，如核提取物中 NF kappa B 的 p50 亚基增加所示。阻断 MAPK 和 NF kappa B 信号传导会降低雌二醇的抗氧化作用。最后，我们发现雌激素激活 MAPK 和 NF kappa B 可驱动抗氧化酶 Mn-SOD 和 GPx 的表达。我们得出结论，雌二醇在受体激活后依次激活 MAPK 和 NF kappa B，从而上调抗氧化酶的表达，这为雌激素的抗氧化特性及其对长寿相关基因的影响提供了令人信服的解释。
Females live longer than males. Oestrogens protect females against aging by up-regulating the expression of antioxidant, longevity-related genes such as glutathione peroxidase (GPx) and Mn-superoxide dismutase (Mn-SOD). The mechanism through which oestrogens up-regulate those enzymes remains unidentified, but may have implications for gender differences in lifespan. We show that physiological concentrations of oestradiol act through oestrogen receptors to reduce peroxide levels in MCF-7 cells (a mammary gland tumour cell line). Oestradiol increases MAP kinase (MAPK) activation as indicated by ERK1 and ERK2 phosphorylation in MCF-7 cells, which in turn activates the nuclear factor kappa B (NF kappa B) signalling pathways as indicated by an increase in the p50 subunit of NF kappa B in nuclear extracts. Blockade of MAPK and NF kappa B signalling reduces the antioxidant effect of oestradiol. Finally, we show that activation of MAPK and NF kappa B by oestrogens drives the expression of the antioxidant enzymes Mn-SOD and GPx. We conclude that oestradiol sequentially activates MAPK and NF kappa B following receptor activation to up-regulate the expression of antioxidant enzymes, providing a cogent explanation for the antioxidant properties of oestrogen and its effects on longevity-related genes.