Overexpression of catalase delays G0/G1- to S-phase transition during cell cycle progression in mouse aortic endothelial cells.
Overexpression of catalase delays G0/G1- to S-phase transition during cell cycle progression in mouse aortic endothelial cells.
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DOI：
10.1016/j.freeradbiomed.2009.03.018
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发表时间：
2009-06-15
影响因子：
7.4
通讯作者：
Guo, ZhongMao
中科院分区：
文献类型：
--
作者：
Onumah, Ogbeyalu E.;Jules, George E.;Zhao, Yanfeng;Zhou, LiChun;Yang, Hong;Guo, ZhongMao
关键词：
虽然我们知道过氧化氢（H2O2）促进细胞增殖，但对其在内皮细胞周期进程中的作用知之甚少。评估内源性H2O2在细胞周期进程中的调节作用；我们研究了过度表达人过氧化氢酶转基因（hCatTg）的小鼠主动脉内皮细胞（MAECs）的细胞周期进程，该基因可以破坏H2O2。与野生型对照相比，hCatTg MAECs的生长时间延长了一倍（44.0±4.7 h比28.6±0.8 h, p<0.05），与生长速度和H2O2释放减少一致。用氨基三唑（一种过氧化氢酶抑制剂）孵育，可以防止hCatTg maec生长速度下降。用氨三唑抑制过氧化氢酶活性可消除过氧化氢酶过表达诱导的抗增殖作用。流式细胞术分析显示，与野生型细胞相比，hCatTg MAECs的G0/G1期延长（25.0±0.9 h比15.9±1.4 h, p<0.05），主要是由于G0/G1期延长。hCatTg MAECs还表现出细胞周期中负责G0/G1到S期转变的周期蛋白依赖性激酶（Cdk）复合物的活性降低，包括周期蛋白D-Cdk4和周期蛋白E-Cdk2复合物。此外，hCatTg MAECs中cyclin-Cdk活性的降低伴随着两种Cdk抑制剂p21和p27蛋白水平的升高，这两种Cdk抑制剂抑制了G0/G1到S期转变所需的Cdk活性。敲低p21和/或p27可减弱过氧化氢酶过表达在maec中的抗增殖作用。这些结果，再加上过氧化氢酶是H2O2的清除剂；提示内源性产生的H2O2通过促进从G0/G1期到S期的过渡介导MAEC增殖。
While it is understood that hydrogen peroxide (H2O2) promotes cellular proliferation, little is known about its role in endothelial cell cycle progression. To assess the regulatory role of endogenously produced H2O2 in cell cycle progression; we studied the cell cycle progression in mouse aortic endothelial cells (MAECs) obtained from mice overexpressing a human catalase transgene (hCatTg), which destroys H2O2. The hCatTg MAECs displayed a prolonged doubling time compared to wild-type controls (44.0 ± 4.7 h versus 28.6 ± 0.8 h, p<0.05), consistent with a diminished growth rate and H2O2 release. Incubation with aminotriazole, a catalase inhibitor, prevented the observed diminished growth rate in hCatTg MAECs. Inhibition of catalase activity with aminotriazole abrogated catalase overexpression-induced antiproliferative action. Flow cytometry analysis indicated that the prolonged doubling time was principally due to an extended G0/G1 phase in hCatTg MAECs, as compared to the wild-type cells (25.0 ± 0.9 h versus 15.9 ± 1.4 h, p<0.05). The hCatTg MAECs also exhibited decreased activities of the cyclin-dependent kinase (Cdk) complexes responsible for G0/G1 to S phase transition in the cell cycle, including cyclin D-Cdk4 and cyclin E-Cdk2 complexes. Moreover, the reduction in cyclin-Cdk activities in hCatTg MAECs was accompanied by increased protein levels of two Cdk inhibitors, p21 and p27, which inhibit the Cdk activity required for the G0/G1 to S phase transition. Knockdown of p21 and/or p27 attenuated the antiproliferative effect of catalase overexpression in MAECs. These results, together with the fact that catalase is an H2O2 scavenger; suggest that endogenously produced H2O2 mediates MAEC proliferation by fostering the transition from G0/G1 to S phase.
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影响因子：
4.1
作者：
Frost, SJ;Simpson, DJ;Farrell, WE
通讯作者：
Farrell, WE
影响因子：
7.4
作者：
OBERLEY, TD;SCHULTZ, JL;OBERLEY, LW
通讯作者：
OBERLEY, LW
DOI：
10.1161/01.atv.0000246777.30819.85
发表时间：
2006-12-01
影响因子：
8.7
作者：
Kappert, Kai;Sparwel, Jan;Ostman, Arne
通讯作者：
Ostman, Arne
影响因子：
--
作者：
Musgrove, EA;Lee, CSL;Sutherland, RL
通讯作者：
Sutherland, RL
影响因子：
8
作者：
Felty, Q;Singh, KP;Roy, D
通讯作者：
Roy, D