p38丝裂原活化蛋白激酶及氧化应激在铜诱导衰老中的作用
Role of p38MAPK and oxidative stress in copper-induced senescence.
作者信息
Boilan Emmanuelle, Winant Virginie, Dumortier Elise, Piret Jean-Pascal, Bonfitto François, Osiewacz Heinz D, Debacq-Chainiaux Florence, Toussaint Olivier
机构信息
NARILIS URBC, University of Namur (FUNDP), 61, rue de Bruxelles, 5000, Namur, Belgium.
出版信息
Age (Dordr). 2013 Dec;35(6):2255-71. doi: 10.1007/s11357-013-9521-3. Epub 2013 Apr 12.
Abstract
In the present work, we indicate that copper is involved in the senescence of human diploid fibroblasts and we describe mechanisms to explain it. Using different techniques, we show for the first time an accumulation of copper in cells during replicative senescence. This accumulation seems to be co-localized with lipofuscin. Second, we observed that an incubation of cells with copper sulfate induced oxidative stress, antioxidant response and premature senescence. Antioxidant molecules reduced the appearance of premature senescence. Third, we found that Nrf2 transcription factor was activated and regulated the expression of genes involved in antioxidant response while p38(MAPK) regulated the appearance of premature senescence.
摘要
在本研究中，我们指出铜与人二倍体成纤维细胞的衰老有关，并描述了解释其作用的机制。通过不同技术，我们首次表明在复制性衰老过程中细胞内铜会积累。这种积累似乎与脂褐素共定位。其次，我们观察到用硫酸铜孵育细胞会诱导氧化应激、抗氧化反应和过早衰老。抗氧化分子减少了过早衰老的出现。第三，我们发现Nrf2转录因子被激活并调节参与抗氧化反应的基因表达，而p38（丝裂原活化蛋白激酶）调节过早衰老的出现。
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