酸诱导动态核蛋白频谱变化和DNA-蛋白质交叉链接,p97介导修复
Jin Cheng1,2, Haoyin Liu1, Wenpei Yu1
1Department of Chemical Defense Medicine, School of Preventive Medicine, The Third Military Medical University Army Medical University, Chongqing, China.
Heliyon
|September 18, 2024
概括
酸会导致显著的核蛋白变化和DNA损伤. 蛋白质p97在暴露后修复这些影响方面发挥着至关重要的作用,涉及DVC1和蛋白酶体.
科学领域:
- 蛋白质组学是指蛋白质组学.
- 细胞生物学 细胞生物学
- 对DNA损伤的反应反应
背景情况:
- 酸 (NM) 是一种化学治疗剂,以化蛋白质和DNA而闻名,导致细胞损伤.
- 之前没有报道过由NM诱导的动态蛋白质变化.
研究的目的:
- 为了研究16HBE细胞在急性末 (NM) 暴露和随后的修复后的动态蛋白质变化.
- 阐明蛋白质p97在NM诱导损伤后的细胞反应和修复机制中的作用.
主要方法:
- 在16HBE细胞中建立了NM的急性 (1小时) 和修复性 (24小时) 暴露模型.
- 分析了核蛋白频谱,DNA-蛋白交联 (DPC) 和DNA损伤标记 (H2AX).
- 利用siRNA对抗p97 (si-p97) 和DVC1,以及蛋白酶体抑制剂MG132来评估它们的功能作用.
主要成果:
- 急性NM暴露导致了核蛋白质概况的显著变化,增加了核蛋白质的流入,DNA-蛋白质交联 (DPC) 和DNA双链断裂 (通过H2AX酸化表示).
- 抑制p97 (si-p97) 损害了蛋白质表达特征的恢复,并在修复阶段加剧了DNA损伤标记.
- si-p97和si-DVC1治疗增加了细胞质蛋白酶体 (PSMD2) 水平,这表明它在蛋白质降解途径中发挥了作用.
结论:
- 急性NM暴露会诱导快速和严重的核蛋白质变化,DNA损伤和DPC形成.
- p97对于维持核蛋白常态稳定和促进NM暴露后DPC去除至关重要.
- 在NM损伤修复中,p97的功能涉及DVC1和蛋白酶体系统的参与.
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