蛋白质S-palmitoylation增强了对的反应中的profibrotic信号传递
Choon-Myung Lee1, Zachery R Jarrell1, Ho Young Lee1
1Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, GA 30322, USA.
Toxicology and applied pharmacology
|January 9, 2024
概括
暴露会增加蛋白质棕化,增强细胞吸收和肺部纤维信号传递. 用2-棕酸盐 (2-BP) 抑制这一过程,可能为治疗引起的肺病提供一种治疗策略.
科学领域:
- 环境健康 环境健康
- 分子生物学分子生物学
- 毒理学 毒理学 毒理学
背景情况:
- (Cd) 是一种有毒金属,由于排泄效率低下,它会在人体中积累.
- 暴露于Cd会影响肺细胞的新陈代谢和增殖,有助于益纤维细胞反应.
- 此前,zDHHC11转录已被确定为Cd反应中的关键参与者.
研究的目的:
- 调查蛋白质S-palmitoylation在毒性中的作用.
- 为了确定是否影响蛋白质棕化通路.
- 探索抑制诱导的肺纤维化中的棕代谢的治疗潜力.
主要方法:
- 人类肺纤维细胞用和2-棕酸盐 (2-BP),一种棕转移酶抑制剂进行治疗.
- 基于质谱的蛋白质组学识别了棕细胞化蛋白质.
- 用基因表达分析来评估纤维化标记物和TGF-β信号传递.
主要成果:
- 暴露增加了肺纤维细胞中的蛋白S-palmitoylation.
- 2-BP抑制了诱导的蛋白质棕化,细胞吸收和ZIP14载体棕化.
- 诱导的TGF-β1,TGF-β3和纤维化标志物 (α-SMA,MMP-2,COL1A1) 的表达被2-BP阻断.
- 2-BP还抑制了TGF-β1依赖蛋白的棕化.
结论:
- 蛋白质S-palmitoylation是毒性的关键机制.
- 棕化增强了细胞中的积,并支持TGF-β1依赖的纤维化信号传递.
- 抑制蛋白棕化可能是引起的肺纤维化的一种新疗法.
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