Differential regulation of phosphatidylinositol 3-kinase/Akt, mitogen-activated protein kinase, and AMP-activated protein kinase pathways during menadione-induced oxidative stress in the kidney of young and old rats
Differential regulation of phosphatidylinositol 3-kinase/Akt, mitogen-activated protein kinase, and AMP-activated protein kinase pathways during menadione-induced oxidative stress in the kidney of young and old rats
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DOI：
10.1016/j.bbrc.2004.01.093
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发表时间：
2004-03-12
影响因子：
3.1
通讯作者：
Kang, I
中科院分区：
文献类型：
--
作者：
Jin, QR;Jhun, BS;Kang, I
我们研究了幼年和老年大鼠肾脏氧化应激过程中各种信号转导通路的调节。在青年组(2个月)和老年组(24个月)，观察了甲奈二酮对PI-3-K、MAPK和AMPK通路分子的调节作用。与青年组相比，老年组PI-3-K活性和Akt磷酸化水平显著降低。PTEN抑癌基因在老年组的表达和磷酸化水平也较低。PI3-激酶途径中的分子对甲奈二酮的反应最小。相反，在两组中均观察到甲萘二酮对ERK1/2的磷酸化诱导5倍以上。另一方面，老年组JNK1和AMPK的基础活性以及甲萘二酮诱导的活性均高于青年组。两组的p27(Kip1)、P53和p21(Waf1)均略有升高，但老年组的基础诱导水平明显高于老年组。综上所述，这些结果提示PI3K/Akt通路的增龄性下调和JNK1、AMPK和P53通路的上调可能与氧化应激易感性增加有关。(C)2004 Elsevier Inc.保留所有权利。
We investigated regulation of various signal transduction pathways during oxidative stresses in the kidney of young and aged rats. Menadione-induced regulation of molecules in PI 3-kinase, MAPK, and AMPK pathways was determined in the young (2 months) and old (24 months) groups. PI 3-kinase activity and Akt phosphorylation were significantly reduced in the old compared with the young. PTEN tumor suppressor was also lower in its expression and phosphorylation levels in the old. Response of the molecules in PI 3-kinase pathway to menadione was minimized. In contrast, over 5-fold induction of ERK1/2 phosphorylation by menadione was observed in both groups. On the other hand, basal activities as well as menadione-induced activities of JNK1 and AMPK were higher in the old than in the young. While p27(Kip1), p53, and p21(Waf1) were slightly increased by menadione in both groups, the basal induction level in the old was considerably higher. In conclusion, the results suggest that the age-related down-regulation of PI 3-kinase/Akt pathway and up-regulation of JNK1, AMPK, and p53 pathways may be responsible for the increased susceptibility to oxidative stress. (C) 2004 Elsevier Inc. All rights reserved.