脂肪毒性通过激活 STING 通路诱导心肌细胞铁变态反应

IF 5.9 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Qian Chen, Yina Wang, Jiafu Wang, Xiaolan Ouyang, Junlin Zhong, Yao Huang, Zhuoshan Huang, Benrong Zheng, Long Peng, Xixiang Tang, Suhua Li
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引用次数: 0

摘要

目的 脂肪毒性是导致心肌细胞死亡和心脏损伤的一个公认因素,而铁蛋白沉积被认为是心肌细胞疾病的一个关键死亡模式。本研究旨在探讨铁蛋白沉积在脂肪毒性诱导的心肌损伤中的潜在作用和机制。方法 建立八周高脂饮食 SD 大鼠和用棕榈酸(PA)处理的 H9c2 心肌细胞的体内和体外脂肪毒性模型。铁前列素-1(Fer-1)和脂肪前列素-1(Lip-1)被用来抑制铁蛋白沉积。进一步引入了心肌特异性 STING 基因敲除大鼠(Stingmyo-KD)与高密度脂蛋白胆固醇。检测H9c2细胞/心肌中大鼠心脏结构和功能、细胞活力、脂质过氧化水平、丙二醛(MDA)、谷胱甘肽(GSH)、线粒体功能、铁蛋白沉积相关蛋白和STING通路相关蛋白。结果 服用铁蛋白沉积抑制剂的高脂血症大鼠的心脏结构和功能得到改善,脂质过氧化反应减少,GSH 恢复,这在 H9c2 细胞中得到进一步证实。在 PA 刺激下,STING 通路的激活具有时间依赖性。敲除 STING 的表达可减少 PA 诱导的细胞死亡、脂质过氧化和 MDA 水平,同时恢复 GSH。此外,STING 抑制剂抑制的 HFD Stingmyo-KD 大鼠和系统性抑制的 HFD 大鼠均表现出减轻脂肪毒性诱导的心肌铁蛋白沉着,减少心肌损伤。创新与结论 这些研究结果表明,脂肪毒性可通过激活 STING 通路诱导心肌细胞铁变态反应,为脂肪毒性心肌病的治疗提供了新的靶点和策略。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Lipotoxicity Induces Cardiomyocyte Ferroptosis via Activating the STING Pathway.
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来源期刊
Antioxidants & redox signaling
Antioxidants & redox signaling 生物-内分泌学与代谢
CiteScore
14.10
自引率
1.50%
发文量
170
审稿时长
3-6 weeks
期刊介绍: Antioxidants & Redox Signaling (ARS) is the leading peer-reviewed journal dedicated to understanding the vital impact of oxygen and oxidation-reduction (redox) processes on human health and disease. The Journal explores key issues in genetic, pharmaceutical, and nutritional redox-based therapeutics. Cutting-edge research focuses on structural biology, stem cells, regenerative medicine, epigenetics, imaging, clinical outcomes, and preventive and therapeutic nutrition, among other areas. ARS has expanded to create two unique foci within one journal: ARS Discoveries and ARS Therapeutics. ARS Discoveries (24 issues) publishes the highest-caliber breakthroughs in basic and applied research. ARS Therapeutics (12 issues) is the first publication of its kind that will help enhance the entire field of redox biology by showcasing the potential of redox sciences to change health outcomes. ARS coverage includes: -ROS/RNS as messengers -Gaseous signal transducers -Hypoxia and tissue oxygenation -microRNA -Prokaryotic systems -Lessons from plant biology
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