关键词: Aspergillus medius Ferroptosis Immunostimulatory effect Polysaccharide Structural characterization

Mesh : Animals Mice NF-E2-Related Factor 2 Ferroptosis Aspergillus / chemistry Polysaccharides / chemistry RAW 264.7 Cells Immunity Immunomodulation Carbon Adenosine Monophosphate / analogs & derivatives Thionucleotides

来  源:   DOI:10.1016/j.ijbiomac.2024.130703

Abstract:
Marine fungal exopolysaccharides play a crucial role in immunoregulation. In this investigation, a novel polysaccharide was extracted from the culture medium of the marine fungus Aspergillus medius SCAU-236. Compositional analysis revealed a structure composed of glucose units with (1,4)-α-D-Glcp, (1,3,4)-β-D-Glcp, and (1,4,6)-α-D-Glcp, along with side chains of 1-α-D-Glcp linked to carbon 6 of (1,4,6)-α-D-Glcp and carbon 3 of (1,3,4)-β-D-Glcp. Functional evaluations on RAW264.7 macrophage cells demonstrated Aspergillus medius polysaccharide (ASMP)\'s effects on cell proliferation, nitric oxide levels, and the secretion of TNF-α, IL-6, and IL-1β cytokines. Additionally, metabolomics indicated ASMP\'s potential to modulate macrophage immune function by impacting key regulatory molecules, including COX-2, iNOS, Nrf2, SLC7A11, GPX4, and ACSL4. The Nrf2/SLC7A11/GPX4 axis and ACSL4 were suggested to be involved in ASMP-induced ferroptosis, leading to increased reactive oxygen species (ROS) levels and lipid peroxidation. These findings propose a unique mechanism by which ASMP exerts immunomodulatory effects through ferroptosis induction, contributing to the understanding of marine-derived compounds in immunomodulation research.
摘要:
海洋真菌胞外多糖在免疫调节中起着至关重要的作用。在这次调查中,从海洋真菌曲霉SCAU-236的培养基中提取了一种新型多糖。组成分析揭示了由具有(1,4)-α-D-Glcp的葡萄糖单元组成的结构,(1,3,4)-β-D-Glcp,和(1,4,6)-α-D-Glcp,1-α-D-Glcp的侧链与(1,4,6)-α-D-Glcp的碳6和(1,3,4)-β-D-Glcp的碳3连接。对RAW264.7巨噬细胞的功能评估证明了中曲霉多糖(ASMP)对细胞增殖的影响,一氧化氮水平,和TNF-α的分泌,IL-6和IL-1β细胞因子。此外,代谢组学表明ASMP通过影响关键调节分子来调节巨噬细胞免疫功能的潜力,包括COX-2,iNOS,Nrf2、SLC7A11、GPX4和ACSL4。提示Nrf2/SLC7A11/GPX4轴和ACSL4参与ASMP诱导的铁凋亡,导致活性氧(ROS)水平增加和脂质过氧化。这些发现提出了ASMP通过铁凋亡诱导发挥免疫调节作用的独特机制。有助于在免疫调节研究中理解海洋衍生化合物。
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