Agro-Environmental Research Centre, Institute of Environmental Sciences, Hungarian University of Agriculture and Life Sciences, Herman O. út 15, H-1022 Budapest, Hungary.
Nanobiosensorics Laboratory, Institute of Technical Physics and Materials Science, Centre for Energy Research, Konkoly-Thege M. u. 29-33, H-1121 Budapest, Hungary.
Int J Mol Sci. 2022 Oct 17;23(20):12425. doi: 10.3390/ijms232012425.
Transmembrane glycoprotein integrins play crucial roles in biochemical processes, and by their inhibition or activation, different signal pathways can be disrupted, leading to abnormal physiological functions. We have previously demonstrated the inhibitory effect of glyphosate herbicide's active ingredient on cell adhesion and its αvβ3 integrin antagonist effect. Therefore, it appeared particularly exciting to investigate inhibition of glyphosate and its metabolites on a wider range of Arg-Gly-Asp (RGD) binding integrins, namely αvβ3, α5β1 and αllbβ3. Thus, the purpose of this study was to assess how extended the inhibitory effect observed for glyphosate on the integrin αvβ3 is in terms of other RGD integrins and other structurally or metabolically related derivatives of glyphosate. Five different experimental setups using enzyme-linked immunosorbent assays were applied: (i) αvβ3 binding to a synthetic polymer containing RGD; (ii) αvβ3 binding to its extracellular matrix (ECM) protein, vitronectin; (iii) α5β1 binding to the above polymer containing RGD; (iv) αllbβ3 binding to its ECM protein, fibrinogen and (v) αvβ3 binding to the SARS-CoV-2 spike protein receptor binding domain. Total inhibition of αvβ3 binding to RGD was detected for glyphosate and its main metabolite, aminomethylphosphonic acid (AMPA), as well as for acetylglycine on α5β1 binding to RGD.
跨膜糖蛋白整合素在生化过程中发挥着至关重要的作用，通过对其进行抑制或激活，可以破坏不同的信号通路，导致异常的生理功能。我们之前已经证明了草甘膦除草剂的活性成分对细胞黏附的抑制作用及其对αvβ3 整合素的拮抗剂作用。因此，研究草甘膦及其代谢物对更广泛的 Arg-Gly-Asp（RGD）结合整合素，即αvβ3、α5β1 和αllbβ3 的抑制作用，显得尤为令人兴奋。因此，本研究的目的是评估观察到的草甘膦对整合素αvβ3 的抑制作用在其他 RGD 整合素和草甘膦的其他结构或代谢相关衍生物方面的扩展程度。本研究采用了五种不同的酶联免疫吸附试验实验设置：（i）αvβ3 与含有 RGD 的合成聚合物的结合；（ii）αvβ3 与细胞外基质（ECM）蛋白 vitronectin 的结合；（iii）α5β1 与含有 RGD 的上述聚合物的结合；（iv）αllbβ3 与 ECM 蛋白纤维蛋白原的结合；（v）αvβ3 与 SARS-CoV-2 刺突蛋白受体结合域的结合。草甘膦及其主要代谢物氨甲基膦酸（AMPA）以及乙酰甘氨酸对α5β1 与 RGD 的结合均完全抑制了αvβ3 与 RGD 的结合。
