Sirt5通过蛋白质氨酸恶化调节状细胞代谢和骨关节炎的发展
Huanhuan Liu1,2, Anupama Binoy1,2, Siqi Ren1,2
1Department of Biomedical Sciences, Heritage College of Osteopathic Medicine (HCOM), Ohio University, Athens, OH, 45701, USA.
bioRxiv : the preprint server for biology
|August 2, 2024
概括
赛尔图因-5 (SIRT5) 和氨酸恶化 (MaK) 是关键在骨关节炎 (OA) 的发展. 对SIRT5-MaK的失调会加剧衰老和肥胖中的OA,突出了一个新的治疗目标.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 遗传学 是一个遗传学.
背景情况:
- 冠状细胞代谢功能障碍是骨关节炎 (OA) 发病的核心原因,特别是在衰老和肥胖时.
- 蛋白质后翻译性修饰 (PTMs) 调节细胞代谢,而氨酸化 (MaK) 是一个显著的因素.
- 赛尔图因-5 (SIRT5) 是包括MaK在内的PTM的关键调节剂,其在OA中扮演的角色需要调查.
研究的目的:
- 调查氨酸恶化 (MaK) 和其调节剂Sirtuin-5 (SIRT5) 在骨关节炎 (OA) 的发展中的作用.
- 探索Sirt5缺乏和肥胖对关节退化的影响.
- 为了确定与OA相关的SIRT5的遗传变异.
主要方法:
- 在人类和小鼠软骨中分析SIRT5和MaK水平.
- 使用系统性和软骨特异性的Sirt5淘汰赛小鼠模型与高脂肪饮食 (HFD) 诱导.
- 蛋白质组学用于划定细胞中的恶性瘤,并在人类人口数据库中识别SIRT5突变.
主要成果:
- 在衰老的软骨中,SIRT5水平下降,而MaK水平增加.
- 结合Sirt5缺乏和肥胖会以性别依赖的方式恶化关节退化.
- 确定了一种罕见的SIRT5突变 (F101L),在OA家族中分离,导致MaK增加,ECM基因表达减少和炎症增加.
结论:
- 通过Sirt5介导的MaK是冠状细胞代谢的关键调节者.
- Sirt5-MaK通路的失调是衰老和与肥胖相关的OA的一个重要机制.
- 准Sirt5-MaK通路可能为OA提供治疗策略.
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