硫化可以通过S-硫化化-1酶减轻ox-LDL诱导的NLRP3/caspase-1/GSDMD依赖性巨细胞灭
Zhenli Jia1, Xulin Zhang2, Zhiyi Li1
1Ministry of Education Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University, Shihezi, Xinjiang 832003, P.R. China.
Molecular medicine reports
|June 14, 2024
概括
硫化 (H2S) 减轻了巨细胞的灭,这是血管炎症和动脉样硬化的关键驱动因素. H2S通过抑制烧灭酶信号通路并增强caspase-1的S-硫化来实现这一目标.
科学领域:
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
- 心血管研究研究心血管研究
背景情况:
- 巨质炎与血管炎症和动脉样硬化 (AS) 有关.
- 硫化 (H2S) 已显示出对炎症和AS的保护作用.
- 精确的分子机制,H2S调节烧信号仍然不清楚.
研究的目的:
- 调查H2S是否可以减轻由氧化低密度脂蛋白 (ox-LDL) 诱导的巨细胞灭症.
- 阐明H2S在调节烧灭酶信号通路和卡斯帕酶-1的S-硫化中的作用.
主要方法:
- 用H2S供体 (NaHS) 或抑制剂 (PAG) 治疗THP-1衍生的巨细胞,并用ox-LDL刺激.
- 通过显微镜,LDH释放和特定标记物表达 (NLRP3,caspase-1,GSDMD) 来评估热症.
- 量化了卡斯帕酶-1活性,IL-1β,IL-18分泌,以及pro-caspase-1的S-硫化.
主要成果:
- 氧-LDL通过激活活信号通路,显著诱导了巨细胞的活灭亡.
- 外源H2S (NaHS) 通过抑制这种途径,改善了ox-LDL诱导的热亡.
- H2S增加了pro-caspase-1的S-硫化,减少了caspase-1的活性和下游的炎症性细胞因子释放.
结论:
- H2S有效地抑制了由ox-LDL诱导的巨细胞灭.
- 该机制涉及降低激素灭菌信号通路的调节,并增加pro-caspase-1 S-sulfhydration.
- 这项研究揭示了H2S在对抗动脉样硬化的新型分子机制.
相关概念视频
01:17Phagocytosis of Apoptotic Cells
3.8K
Cells undergoing apoptosis form apoptotic bodies that must be removed immediately to prevent inflammation, autoimmune diseases, and necrosis. Phagocytosis is carried out by professional phagocytes such as macrophages or immature dendritic cells. Non-professional phagocytes such as epithelial cells and fibroblasts also take part in this process; however, they are not as effective as professional phagocytes.
Normal cells contain receptors that prevent them from being recognized...
Normal cells contain receptors that prevent them from being recognized...
3.8K
01:24Caspases
12.4K
Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside...
12.4K
01:17The Extrinsic Apoptotic Pathway
6.3K
The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
6.3K
01:31The Intrinsic Apoptotic Pathway
6.5K
Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
6.5K
01:30Overview of Cell Death
7.2K
Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the...
7.2K