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A High-Throughput Comet Assay Approach for Assessing Cellular DNA Damage
Published on: May 10, 2022
齐斯普拉丁与人体超氧化物脱酶的相互作用
Lucia Banci1, Ivano Bertini, Olga Blaževitš
1Magnetic Resonance Center CERM, University of Florence, Via Luigi Sacconi 6, 50019 Sesto Fiorentino, Florence, Italy. banci@cerm.unifi.it
Journal of the American Chemical Society
|April 5, 2012
概括
西斯普拉丁与人体超氧化物脱酶 (hSOD1) 结合,防止其聚合并溶解现有的块. 这表明cisplatin是可以使用的.
科学领域:
- 生物化学 生物化学
- 神经科学是一个神经科学.
- 药理学 药理学是指药理学的学科.
背景情况:
- 肌缩侧面硬化症 (ALS) 是一种神经退行性疾病,其特征是错误折叠的蛋白质的聚合,特别是人体超氧化物失突酶 (hSOD1).
- 氧化和脱金属形式的hSOD1容易聚合,从而导致ALS的发病.
研究的目的:
- 调查西斯普拉丁与人类超氧化物脱酶 (hSOD1) 的相互作用.
- 评估西斯普拉丁在预防和逆转hSOD1聚合方面的潜力,这是ALS的一个标志.
主要方法:
- 研究了思丁与hSOD1的各种形式的结合,包括二硫化物氧化的apo形式.
- 确定了西斯-hSOD1相互作用的解离常数.
- 在体外和细胞模型中评估了思丁对脱金属化氧化hSOD1的聚合,溶解和单体化的作用.
主要成果:
- 西斯普拉丁与hSOD1的二硫化氧化阿波形式结合,解离常数为37±3μM,特别是与氨酸111 (Cys111) 相互作用.
- 西斯丁还与Cu(2) - Zn(2) 和 Zn(2) - Zn(2) 形式的hSOD1.2结合.
- 西斯普拉丁有效地抑制了脱金属化氧化hSOD1的聚合,并在体外和细胞内溶解现有的hSOD1寡合体.
结论:
- 西斯普拉丁显示出作为治疗性化合物的显著潜力,用于肌缩侧面硬化症 (ALS).
- 它与hSOD1聚合物相互作用和破坏的能力为ALS提供了一个新的治疗策略.
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