The impact of frequently used herbicides in argentina, on cell lines

Authors

  • Calén N. Sansalon Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3), Departamento de Fisiología, Biología Molecular y Celular (DFBMC), Facultad de Ciencias Exactas y Naturales (FCEyN), Universidad de Buenos Aires (UBA), Buenos Aires, Argentina. Author https://orcid.org/0009-0003-4832-6026
  • Facundo Couto Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3), Departamento de Fisiología, Biología Molecular y Celular (DFBMC), Facultad de Ciencias Exactas y Naturales (FCEyN), Universidad de Buenos Aires (UBA), Buenos Aires, Argentina. Author https://orcid.org/0009-0002-1787-6538
  • Matías Blaustein Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Argentina. Author https://orcid.org/0000-0001-6309-6888
  • Mercedes García Carrillo Instituto de Biociencias, Biotecnología y Biología Traslacional (iB3), Departamento de Fisiología, Biología Molecular y Celular (DFBMC), Facultad de Ciencias Exactas y Naturales (FCEyN), Universidad de Buenos Aires (UBA), Buenos Aires, Argentina. Author https://orcid.org/0000-0001-7868-6047

DOI:

https://doi.org/10.56294/piii2024278

Keywords:

Herbicides, UPR, Akt, Paraquat, Atrazine, Glyphosate

Abstract

The use of herbicides worldwide is currently the subject of debate both within the scientific community and among the general public, focusing on their potential adverse effects on
human health. However, there are few studies on the molecular and cellular changes produced by herbicides.(1-5)
In this work, it was proposed to advance in the understanding of the cell signaling pathways affected by exposure to three herbicide formulations: RoundUp (RU, a.i.: glyphosate), Gesaprim (GS, a.i.: atrazine) and Paraquat Insuagro (PI, a.i.: paraquat). In particular, it was studied the effects of exposure to these formulations on the response to misfolded proteins or UPR, and the PI3K/Akt pathway in the HeLa Kyoto cell line. Dysregulation of these pathways has been reported to be associated with various malignancies.
For all in vitro herbicide exposure assays, concentrations below the recommended application limit were chosen to evaluate the effect, on different exposure times on the regulation of both pathways.(6-14) For these purposes, western blot and fluorescence microscopy techniques were used.
Results revealed activation of all three branches of the UPR (ATF6, PERK and IRE1) in those cells exposed to PI. On the other hand, ATF6 was activated as a result of GS exposure. In the case of RU, dysregulation of the PI3K/Akt pathway was observed, without detecting changes in the UPR. In conclusion, exposure of HeLa Kyoto cells to different herbicides leads to dysregulation of both the UPR and the PI3K/Akt pathway

References

Caudle, W. M. Occupational exposures and parkinsonism. Handbook of clinical neurology. 2015;131,225-239.

Park, S. E., Lim, S. R., Choi, H. K., & Bae, J. Triazine herbicides inhibit relaxin signaling and disrupt nitric oxide homeostasis. Toxicology and applied pharmacology.

;307,10-18.

Benbrook, C. M. How did the US EPA and IARC reach diametrically opposed conclusions on the genotoxicity of glyphosate-based herbicides?. Environmental Sciences Europe. 2019;31(1),1-16.

Huang, P., Yang, J., Ning, J., Wang, M., & Song, Q. Atrazine triggers DNA damage response and induces DNA double-strand breaks in MCF-10A cells. International journal of molecular sciences. 2015;16(7),14353-14368.

Wang, S., Zhang, Q., Zheng, S., Chen, M., Zhao, F., & Xu, S. Atrazine exposure triggers common carp neutrophil apoptosis via the CYP450s/ROS pathway. Fish & shellfish immunology. 2019;84,551-557.

Altomare, D. A., & Testa, J. R. Perturbations of the AKT signaling pathway in human cancer. Oncogene. 2005;24(50),7455.

Walter, P., & Ron, D. The unfolded protein response: from stress pathway to homeostatic regulation. Science. 2011;334(6059),1081-1086.

Blaustein, M., Pelisch, F., Tanos, T., Munoz, M. J., Wengier, D., Quadrana, L., & Coso, O. A. Concerted regulation of nuclear and cytoplasmic activities of SR proteins by AKT. Nature structural & molecular biology. 2005;12(12),1037.

Blaustein, M., Pelisch, F., & Srebrow, A. Signals, pathways and splicing regulation. The international journal of biochemistry & cell biology. 2007;39(11),2031-2048.

Blaustein, M., Quadrana, L., Risso, G., Mata, M. D. L., Pelisch, F., & Srebrow, A. SF2/ASF regulates proteomic diversity by affecting the balance between translation initiation mechanisms. Journal of cellular biochemistry. 2009;107(4),826-833.

Riggio, M., Polo, M. L., Blaustein, M., Colman-Lerner, A., Lüthy, I., Lanari, C., & Novaro, V. PI3K/AKT pathway regulates phosphorylation of steroid receptors, hormone independence and tumor differentiation in breast cancer. Carcinogenesis. 2011;33(3),509-518.

Risso, G., Pelisch, F., Pozzi, B., Mammi, P., Blaustein, M., Colman-Lerner, A., & Srebrow, A. Modification of Akt by SUMO conjugation regulates alternative splicing and cell cycle. Cell Cycle. 2013;12(19),3354-3363.

Blaustein, M., Pérez-Munizaga, D., Sánchez, M. A., Urrutia, C., Grande, A., Risso, G., & Colman-Lerner, A. Modulation of the Akt pathway reveals a novel link with PERK/eIF2α, which is relevant during hypoxia. PloS one. 2013;8(7),e69668.

Blaustein, M. AKT. Encyclopedia of Signaling Molecules. 2018;267-280.

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Published

2024-05-03

How to Cite

1.
Sansalon CN, Couto F, Blaustein M, García Carrillo M. The impact of frequently used herbicides in argentina, on cell lines. SCT Proceedings in Interdisciplinary Insights and Innovations [Internet]. 2024 May 3 [cited 2024 Sep. 19];2:278. Available from: https://proceedings.ageditor.ar/index.php/piii/article/view/247