通过调节sirt2以增加细胞内NADPH,NMN部分挽救了cuproptosis
Yingying Zhang1,2, Shuting Qiu1,2, Shihan Shao1,2
1School of Public Health, Hangzhou Normal University, Hangzhou, China.
Scientific reports
|August 21, 2024
概括
尼古丁胺胺单核酸 (NMN) 通过增加保护性NADPH水平并保持铁硫蛋白质,部分地拯救细胞免受铜诱导的细胞死亡 (亡). 这发生在通过素2 (SIRT2) 的上调,独立于其胺酶活性.
科学领域:
- 细胞生物学 细胞生物学
- 疾病的分子机制.
- 生物化学 生物化学
背景情况:
- 型死涉及化蛋白聚合和铁硫 (Fe-S) 蛋白质的损失,影响DNA复制和修复.
- 赛尔图因2和4 (SIRT2,SIRT4) 是利用尼古丁胺胺氨基二核酸 (NAD+) 的胺酶,但它们在亡中的作用尚不清楚.
- 尼古丁胺胺单核酸 (NMN) 是NAD+的前体,正在研究其对cuproptosis敏感性的潜在影响.
研究的目的:
- 为了研究NMN对HeLa细胞中铜诱导的细胞死亡 (cuproptosis) 的作用.
- 阐明NMN影响cuproptosis的分子机制.
- 为了确定NMN是否会在cuproptosis期间影响DNA损伤和Fe-S蛋白水平.
主要方法:
- 在HeLa细胞中使用铜 (Cu) 和 elesclomol (Es) 诱导了cuproptosis.
- 评估了细胞DNA损伤水平.
- NMN治疗以剂量依赖的方式进行.
- 分析了Fe-S蛋白质POLD1,sirtin 2 (SIRT2) 和sirtin 4 (SIRT4) 的表达.
- 测量了细胞降低的尼古丁胺胺氨基二核酸盐 (NADPH) 水平.
- 用NAD+激酶 (NADK) 抑制来评估NADPH的作用.
主要成果:
- Es/Cu治疗显著增加了细胞DNA损伤.
- 在剂量取决的方式,NMN治疗部分地从cuproptosis中拯救了细胞,并减少了DNA损伤.
- NMN上调了POLD1的表达,增加了SIRT2的表达和细胞NADPH水平.
- SIRT2,但不是SIRT4,过度表达部分挽救了cuproptosis和增加了NADPH.
- 抑制NADK消除了NMN和SIRT2.2的保护作用.
结论:
- DNA 损伤是铜诱导细胞死亡 (cuproptosis) 的一个关键特征.
- 通过对SIRT2进行上调,促进细胞内NADPH,并保存Fe-S蛋白质,NMN提供了对cuproptosis的部分保护.
- NMN的保护机制涉及增加NADPH的产生,独立于SIRT2的胺酶活性.
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