褪黑素通过调节SIRT3/FOXO3α/ROS轴并与动脉粥样硬化进程中的细胞凋亡相互作用减轻焦亡。

IF 4.3 2区 生物学 Q1 BIOLOGY
Lin Cong, Xiankun Liu, Yiming Bai, Qin Qin, Lili Zhao, Ying Shi, Yunpeng Bai, Zhigang Guo
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引用次数: 0

摘要

背景:动脉粥样硬化(AS)是导致心血管疾病(CVD)的重要因素,随着全球人口老龄化,其发病率稳步上升。焦亡和凋亡是caspase介导的细胞死亡机制,在AS的发生和发展中起重要作用。人类松果体主要产生褪黑激素(MT),这是一种吲哚胺激素,具有强大的抗氧化、抗焦亡和抗凋亡特性。本研究考察了烟碱对人THP-1巨噬细胞的抗氧化应激和抗焦亡作用。方法:体外用1µM尼古丁诱导THP-1巨噬细胞形成焦亡模型,进行30 mM MT处理。体内给ApoE-/-小鼠0.1 mg/mL尼古丁溶液作为饮用水,1 mg/mL MT溶液以10 mg/kg/d灌胃。观察大鼠焦亡、细胞凋亡及氧化应激的变化。结果:MT下调焦亡,其变化与活性氧(ROS)产生的减少、sirtuin3 (SIRT3)的逆转和叉头盒O3 (FOXO3α)的上调相平行。MT对细胞凋亡也有抑制作用,主要是由caspase-1和caspase-3蛋白相互作用引起的。体内研究证实尼古丁可以加速斑块的形成。此外,MT治疗小鼠的AS病变面积减少。结论:MT通过调节SIRT3/FOXO3α/ROS轴并与细胞凋亡相互作用减轻焦亡。重要的是,我们对巨噬细胞焦亡的抑制途径的理解将使我们能够确定其他新的治疗靶点,这将有助于治疗、预防和降低as相关的死亡率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Melatonin alleviates pyroptosis by regulating the SIRT3/FOXO3α/ROS axis and interacting with apoptosis in Atherosclerosis progression.

Background: Atherosclerosis (AS), a significant contributor to cardiovascular disease (CVD), is steadily rising with the aging of the global population. Pyroptosis and apoptosis, both caspase-mediated cell death mechanisms, play an essential role in the occurrence and progression of AS. The human pineal gland primarily produces melatonin (MT), an indoleamine hormone with powerful anti-oxidative, anti-pyroptotic, and anti-apoptotic properties. This study examined MT's anti-oxidative stress and anti-pyroptotic effects on human THP-1 macrophages treated with nicotine.

Methods: In vitro, THP-1 macrophages were induced by 1 µM nicotine to form a pyroptosis model and performed 30 mM MT for treatment. In vivo, ApoE-/- mice were administered 0.1 mg/mL nicotine solution as drinking water, and 1 mg/mL MT solution was intragastric administrated at 10 mg/kg/day. The changes in pyroptosis, apoptosis, and oxidative stress were detected.

Results: MT downregulated pyroptosis, whose changes were paralleled by a reduction in reactive oxygen species (ROS) production, reversal of sirtuin3 (SIRT3), and Forkhead box O3 (FOXO3α) upregulation. MT also inhibited apoptosis, mainly caused by the interaction of caspase-1 and caspase-3 proteins. Vivo studies confirmed that nicotine could accelerate plaque formation. Moreover, mice treated with MT showed a reduction in AS lesion area.

Conclusions: MT alleviates pyroptosis by regulating the SIRT3/FOXO3α/ROS axis and interacting with apoptosis. Importantly, our understanding of the inhibitory pathways for macrophage pyroptosis will allow us to identify other novel therapeutic targets that will help treat, prevent, and reduce AS-associated mortality.

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来源期刊
Biological Research
Biological Research 生物-生物学
CiteScore
10.10
自引率
0.00%
发文量
33
审稿时长
>12 weeks
期刊介绍: Biological Research is an open access, peer-reviewed journal that encompasses diverse fields of experimental biology, such as biochemistry, bioinformatics, biotechnology, cell biology, cancer, chemical biology, developmental biology, evolutionary biology, genetics, genomics, immunology, marine biology, microbiology, molecular biology, neuroscience, plant biology, physiology, stem cell research, structural biology and systems biology.
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