Enhanced expression of mitochondrial superoxide dismutase leads to prolonged in vivo cell cycle progression and up-regulation of mitochondrial thioredoxin
Enhanced expression of mitochondrial superoxide dismutase leads to prolonged in vivo cell cycle progression and up-regulation of mitochondrial thioredoxin
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DOI：
10.1016/j.freeradbiomed.2010.02.028
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发表时间：
2010-06-01
影响因子：
7.4
通讯作者：
Huang, Ting-Ting
中科院分区：
文献类型：
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作者：
Kim, Aekyong;Joseph, Suman;Huang, Ting-Ting
锰超氧化物歧化酶（MnSOD）是一种重要的线粒体抗氧化酶，MnSOD水平升高已被证明可以通过抑制细胞增殖来部分减少肿瘤生长。对成纤维细胞的研究表明，MnSOD表达的增加延长了G1/S期细胞周期的转换时间，并有利于进入静止状态。为了确定在体内组织再生过程中是否发生相同的效果，我们使用了具有肝脏特异性MnSOD表达的转基因小鼠系统和部分肝切除范例来诱导在肝再生过程中同步的体内细胞增殖。我们表明，在这个实验系统中，MnSOD活性增加2.6倍，导致延迟进入S期，作为测量减少溴脱氧尿苷（BrdU）掺入和增殖细胞核抗原（PCNA）的表达减少。因此，与MnSOD水平基线的对照小鼠相比，肝脏中MnSOD表达增加的转基因小鼠的BrdU阳性细胞减少了23%，PCNA表达显著减弱。MnSOD活性的增加也导致线粒体形式的硫氧还蛋白（硫氧还蛋白2）的增加，但不是在其他几种过氧化物酶检查，这表明硫氧还蛋白2在维持线粒体中的氧化还原平衡的重要性与MnSOD水平升高。爱思唯尔公司出版
Mn superoxide dismutase (MnSOD) is an important mitochondrial antioxidant enzyme, and elevated MnSOD levels have been shown to reduce tumor growth in part by suppressing cell proliferation. Studies with fibroblasts have shown that increased MnSOD expression prolongs cell cycle transition time in G1/S and favors entrance into the quiescent state. To determine if the same effect occurs during tissue regeneration in vivo, we used a transgenic mouse system with liver-specific MnSOD expression and a partial hepatectomy paradigm to induce synchronized in vivo cell proliferation during liver regeneration. We show in this experimental system that a 2.6-fold increase in MnSOD activity leads to delayed entry into S phase, as measured by reduction in bromodeoxyuridine (BrdU) incorporation and decreased expression of proliferative cell nuclear antigen (PCNA). Thus, compared to control mice with baseline MnSOD levels, transgenic mice with increased MnSOD expression in the liver have 23% fewer BrdU-positive cells and a marked attenuation of PCNA expression. The increase in MnSOD activity also leads to an increase in the mitochondrial form of thioredoxin (thioredoxin 2), but not in several other peroxidases examined, suggesting the importance of thioredoxin 2 in maintaining redox balance in mitochondria with elevated levels of MnSOD. Published by Elsevier Inc.