Reactive oxygen species control senescence-associated matrix metalloproteinase-1 through c-Jun-N-terminal kinase.
Reactive oxygen species control senescence-associated matrix metalloproteinase-1 through c-Jun-N-terminal kinase.
复制标题
DOI：
10.1002/jcp.22193
复制
发表时间：
2010-10
影响因子：
5.6
通讯作者：
Melendezi, J. Andres
中科院分区：
文献类型：
--
作者：
Dasgupta, Jaya;Kar, Supriya;Liu, Rong;Joseph, Joy;Kalyanaraman, Balaraman;Remington, S. James;Chen, Ceshi;Melendezi, J. Andres
生物体终生暴露在氧化应激下会影响许多衰老过程，其中包括细胞外基质的周转。在这项研究中，我们确定了驱动衰老相关(SA)基质金属蛋白酶-1(MMP-1)表达的氧化还原响应分子信号。精确的生化监测显示，与年轻细胞相比，衰老的成纤维细胞的稳态[H_2O_2]增加了3.5倍(13.7→48.6 PM)。通过低氧暴露或抗氧化剂处理限制过氧化氢的产生可阻止SA增加基质金属蛋白酶-1的表达。依赖H_2O_2对SA-MMP1的调控归因于持续的JNK激活和c-Jun对MMP1启动子的募集。SA JNK的激活对应于其激活激酶(MKK-4)和抑制性磷酸酶(MKP-1)水平的升高和降低。增强的MKP-1表达抵消了SA增加的JNK磷酸化和基质金属蛋白酶-1的产生。总体而言，这些研究定义了氧化还原敏感的信号网络，调节SA基质金属蛋白酶-1的表达，并将衰老的自由基理论与启动异常的基质周转联系起来。
The lifetime exposure of organisms to oxidative stress influences many aging processes which involve the turnover of the extracellular matrix. In this study, we identify the redox-responsive molecular signals that drive senescence-associated (SA) matrix metalloproteinase-1 (MMP-1) expression. Precise biochemical monitoring revealed that senescent fibroblasts increase steady-state [H2O2] 3.5 fold (13.7→48.6 pM) relative to young cells. Restricting H2O2 production through low O2 exposure or by antioxidant treatments prevented SA increases in MMP-1 expression. The H2O2-dependent control of SA MMP-1 is attributed to sustained JNK activation and c-jun recruitment to the MMP-1 promoter. SA JNK activation corresponds to increases and decreases in the levels of its activating kinase (MKK-4) and inhibitory phosphatase (MKP-1), respectively. Enforced MKP-1 expression negates SA increases in JNK phosphorylation and MMP-1 production. Overall, these studies define redox-sensitive signaling networks regulating SA MMP-1 expression and link the free radical theory of aging to initiation of aberrant matrix turnover.
登录
查看更多内容
影响因子：
4.8
作者：
Liu, Rong;Zheng, Han-Qiu;Chen, Ceshi
通讯作者：
Chen, Ceshi
影响因子：
3.9
作者：
KUMAR, S;VINCI, JM;BAGLIONI, C
通讯作者：
BAGLIONI, C
影响因子：
8
作者：
Chen, YR;Shrivastava, A;Tan, TH
通讯作者：
Tan, TH
影响因子：
4.1
作者：
Fleming, Y;Armstrong, CG;Cohen, P
通讯作者：
Cohen, P
影响因子：
3.9
作者：
MILLIS, AJT;MCCUE, HM;BAGLIONI, C
通讯作者：
BAGLIONI, C