Manganese superoxide dismutase protects the proliferative capacity of confluent normal human fibroblasts
Manganese superoxide dismutase protects the proliferative capacity of confluent normal human fibroblasts
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DOI：
10.1074/jbc.m501939200
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发表时间：
2005-05-06
影响因子：
4.8
通讯作者：
Goswami, PC
中科院分区：
文献类型：
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作者：
Sarsour, EH;Agarwal, M;Goswami, PC
我们测试的假设，锰超氧化物歧化酶（MnSOD），抗氧化酶，调节融合的人成纤维细胞的增殖潜力。正常人皮肤（AG 01522）和肺（WI 38，CCL-75）成纤维细胞保持汇合（> 95%G（0）/G（1）），40 - 60天后它们重新进入增殖周期的能力显著降低。再进入的抑制伴随着融合培养物中p16蛋白水平的年龄依赖性增加。在融合生长过程中，腺病毒介导的MnSOD过表达抑制了p16，增强了p21蛋白的积累，并保护成纤维细胞免受增殖潜力丧失的影响。MnSOD过表达融合成纤维细胞中p21蛋白水平的增加与p53蛋白水平无关。p53蛋白水平在对照、含有无插入载体的复制缺陷型腺病毒（AdBgl II）或培养20天和60天的AdMnSOD感染的汇合细胞中没有变化。此外，MnSOD诱导的融合成纤维细胞的增殖能力的保护是独立的端粒酶活性。然而，端粒酶转化的成纤维细胞融合生长MnSOD表达增加，保持其能力，重新进入增殖周期。虽然从60天的汇合控制，AdBgl II-，和AdMnSOD感染的成纤维细胞传代培养的细胞中的视网膜母细胞瘤蛋白的失活是相同的，只有MnSOD过表达的细胞表现出较高的S期的百分比。这些结果支持氧化还原敏感性检查点调节成纤维细胞从G（0）/G（1）到S期的进展的假设。
We tested the hypothesis that manganese superoxide dismutase (MnSOD), an antioxidant enzyme, regulates the proliferative potential of confluent human fibroblasts. Normal human skin ( AG01522) and lung (WI38, CCL-75) fibroblasts kept in confluence (> 95% G(0)/G(1)) showed a significant decrease in their capacity to reenter the proliferation cycle after 40 - 60 days. The inhibition of re-entry was accompanied with the age-dependent increase of p16 protein levels in the confluent culture. Adenoviral mediated overexpression of MnSOD during confluent growth suppressed p16, enhanced p21 protein accumulation, and protected fibroblasts against the loss of proliferation potential. Increases in p21 protein levels in MnSOD overexpressing confluent fibroblasts were independent of p53 protein levels. p53 protein levels did not change in control, replication-defective adenovirus containing an insertless vector (AdBgl II), or AdMnSOD-infected confluent cells cultured for 20 and 60 days. In addition, MnSOD-induced protection of the proliferation capacity of confluent fibroblasts was independent of their telomerase activity. However, telomerase-transformed fibroblasts showed increased MnSOD expression in confluent growth, maintaining their capacity to re-enter the proliferation cycle. Although inactivation of the retinoblastoma protein in cells subcultured from the 60-day confluent control, AdBgl II-, and AdMnSOD-infected fibroblasts was identical, only MnSOD-overexpressing cells showed a higher percentage of S-phase. These results support the hypothesis that a redox-sensitive checkpoint regulated the progression of fibroblasts from G(0)/G(1) to S-phase.