叉头转录因子FOXO3a保护静止细胞免受氧化应激的影响
Geert J P L Kops1, Tobias B Dansen, Paulien E Polderman
1Department of Physiological Chemistry, University Medical Center Utrecht and Center for Biomedical Genetics, 3584 CG Utrecht, The Netherlands.
Nature
|September 20, 2002
概括
静止细胞使用FOXO3a转录因子来增加超氧化物脱酶 (MnSOD),并保护其免受氧化应激. 这种独立于蛋白激酶B (PKB) 的机制增强了细胞存活率,可能与寿命有关.
科学领域:
- 细胞生物学 细胞生物学
- 细胞死亡的分子机制
- 氧化应激和衰老的作用
背景情况:
- 反应性氧物种 (ROS) 对于细胞增殖至关重要,但可以触发细胞亡.
- 蛋白激酶B (PKB) 的激活可以保护增殖细胞免受ROS诱导的亡.
- 保护缺乏PKB活性的静止细胞免受ROS诱导的亡的机制尚不清楚.
研究的目的:
- 为了研究缺乏PKB活性的静止细胞是如何受到反应性氧物种诱导的细胞死亡的保护.
- 阐明叉头转录因子FOXO3a在静止细胞中对氧化应激的细胞保护中的作用.
主要方法:
- 在氧化应激条件下研究了FOXO3a在静止细胞中的作用.
- 评估FOXO3a对超氧化物脱酶 (MnSOD) mRNA和蛋白质水平的影响.
- 研究了PKB无活性,FOXO3a激活和MnSOD表达之间的关系.
主要成果:
- 在静止细胞中,FOXO3a直接增加超氧化物脱酶 (MnSOD) mRNA和蛋白质,增强对氧化应激的抵抗力.
- 这种FOXO3a介导的MnSOD上调可以抵消由葡萄糖剥夺引起的亡.
- 静止细胞中的PKB不活性触发了叉头转录因子激活,导致MnSOD转录激活和ROS减少.
结论:
- 通过FOXO3a介导的MnSOD上调是静止哺乳动物细胞中抗氧化应激的关键保护机制,独立于PKB信号传递.
- 这种替代途径突显了细胞防御机制对ROS的适应性.
- 这些发现表明,叉头转录因子在调节氧化应激抵抗和跨物种的潜在寿命方面发挥着保留作用,从C. elegans延伸到哺乳动物.
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