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凝集素 CGL 和 MTL 是甘露糖结合凝集素家族的代表,它们在伯基特淋巴瘤细胞中表现出不同的抗增殖活性。

Lectins CGL and MTL, representatives of mytilectin family, exhibit different antiproliferative activity in Burkitt's lymphoma cells.

机构信息

G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of Russian Academy of Sciences, Vladivostok, Russia.

Federal Scientific Center of the East Asia Terrestrial Biodiversity, Far Eastern Branch of Russian Academy of Sciences, Vladivostok, Russia.

出版信息

IUBMB Life. 2024 Dec;76(12):1279-1294. doi: 10.1002/iub.2909. Epub 2024 Aug 21.

Abstract

Lectins are carbohydrate-binding proteins, whose biological effects are exerted via binding to glycoconjugates expressed on the surface of cells. Exposure to lectins can lead not only to a change in the structure and properties of cells but also to their death. Here, we studied the biological activity of lectins from the mussels Crenomytilus graynus (CGL) and Mytilus trossulus (MTL) and showed that these proteins can affect the proliferation of human lymphoma cells. Both lectins suppressed the formation of colonies as well as cell cycle progression. The mechanism of action of these lectins was not mediated by reactive oxygen species but included damaging of mitochondria, inhibition of key cell cycle points, and activation of MAPK signaling pathway in tumor cells. Computer modeling suggested that various effects of CGL and MTL on lymphoma cells may be due to the difference in the energy of binding of these lectins to carbohydrate ligands on the cell surface. Thus, molecular recognition of residues of terminal carbohydrates on the surface of tumor cells is a key factor in the manifestation of the biological action of lectins.

摘要

凝集素是一类糖结合蛋白,其生物效应是通过与细胞表面表达的糖缀合物结合来发挥的。凝集素的暴露不仅会导致细胞结构和性质的改变,还会导致细胞死亡。在这里,我们研究了贻贝 Crenomytilus graynus(CGL)和贻贝 Mytilus trossulus(MTL)中的凝集素的生物学活性,并表明这些蛋白质可以影响人类淋巴瘤细胞的增殖。两种凝集素都抑制了集落的形成和细胞周期的进展。这些凝集素的作用机制不是通过活性氧介导的,而是包括损伤线粒体、抑制细胞周期关键节点以及激活肿瘤细胞中的 MAPK 信号通路。计算机建模表明,CGL 和 MTL 对淋巴瘤细胞的各种影响可能是由于这些凝集素与细胞表面碳水化合物配体结合的能量不同所致。因此,对肿瘤细胞表面末端碳水化合物残基的分子识别是凝集素生物学作用表现的关键因素。

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