N-3-oxo-dodecanoyl-L-Homoserine lactone (3-oxo-C12-HSL), as a quorum-sensing (QS) molecule produced by Gram-negative bacteria in the gastrointestinal tract, is a major inducer of oxidative stress indicated by a high level of intracellular reactive oxygen species (ROS)[1].
In vitro, 100μM 3-oxo-C12 HSL elevates intracellular free calcium in platelet, and 3-oxo-C12 HSL induces intracellular calcium-dependent ROS generation[2]. In vitro, 3-oxo-12-HSL also significantly inhibited LPS (lipopolysaccharides) induced IL-6 release at 10 μM, while 100 μM reduced IL-6 release by almost 75%[3]. In vitro, treatment of fibroblasts with 50 μM 3O-C12-HSL for 1 or 3 h (in contrast to 10 μM and the control) resulted in a rapid fragmentation of mitochondrial network, as evidenced by decreased mitochondrial length and area and an elevated number of small mitochondria[4]. In addition, 50 μM 3O-C12-HSL increases the cell area and protrusive activity of macrophages[5].
In vivo, Passively sensitized mice that had been treated with 3-oxo-12-HSL (3 mg/kg) 1 h prior to antigen exposure showed a significant (60%) decrease in PCA (passive cutaneous anaphylaxis) response[3].
References:
[1] Tao S, et al. Caspase-1-dependent mechanism mediating the harmful impacts of the quorum-sensing molecule N-(3-oxo-dodecanoyl)-l-homoserine lactone on the intestinal cells. J Cell Physiol. 2019 Apr;234(4):3621-3633.
[2] Yadav VK, et al. Pseudomonas aeruginosa quorum sensing molecule N-3-oxo-dodecanoyl-l-homoserine lactone activates human platelets through intracellular calcium-mediated ROS generation. Int J Med Microbiol. 2018 Oct;308(7):858-864.
[3] Khambati I, et al. The bacterial quorum-sensing molecule, N-3-oxo-dodecanoyl-L-homoserine lactone, inhibits mediator release and chemotaxis of murine mast cells. Inflamm Res. 2017 Mar;66(3):259-268.
[4] Josephson H, et al. Pseudomonas aeruginosa N-3-Oxo-Dodecanoyl-Homoserine Lactone Impacts Mitochondrial Networks Morphology, Energetics, and Proteome in Host Cells. Front Microbiol. 2020 May 25;11:1069.
[5]Holm A, et al. Pseudomonas aeruginosa N-3-oxo-dodecanoyl-homoserine Lactone Elicits Changes in Cell Volume, Morphology, and AQP9 Characteristics in Macrophages. Front Cell Infect Microbiol. 2016 Mar 24;6:32.
N-3-氧代-十二烷酰基-L-单丝氨酸内酯（3-氧代-C12-HSL）作为胃肠道中革兰氏阴性菌产生的群体感应（QS）分子，是由高水平的细胞内活性氧（ROS）指示的氧化应激的主要诱导剂[1]。
在体外，100μM 3-氧代-C12 HSL提高血小板中的细胞内游离钙，3-氧代C12 HSL诱导细胞内钙依赖性ROS的产生[2]。在体外，3-氧代-12-HSL在10μM时也显著抑制LPS（脂多糖）诱导的IL-6释放，而100μM时IL-6释放减少了近75%[3]。在体外，用50μM 3氧代-C12-HSL处理成纤维细胞1或3小时（与10μM和对照相比）导致线粒体网络的快速断裂，线粒体长度和面积减少以及小线粒体数量增加就是明证[4]。此外，50μM 3氧代-C12-HSL可增加巨噬细胞的细胞面积和前突活性[5]。
在体内，在抗原暴露前1小时接受3-氧代-12-HSL（3 mg/kg）治疗的被动致敏小鼠的PCA（被动皮肤过敏反应）反应显著降低（60%）[3]。