Alachlor breaks down intracellular calcium homeostasis and leads to cell cycle arrest through JNK/MAPK and PI3K/AKT signaling mechanisms in bovine mammary gland epithelial cells

Miji Kim, Garam An, Whasun Lim, Gwonhwa Song

Research output: Contribution to journalArticlepeer-review

Abstract

Alachlor is a widely used herbicide for the cultivation of various grains employed as food for cattle. The mechanisms leading to the toxic effects of alachlor on epithelial cells of the bovine mammary gland are not well known. Thus, this study was conducted to clarify the toxicological effects of alachlor on the immortalized epithelial cell line of the bovine mammary gland (MAC-T) cells. After treatment, many factors related to cell viability, proliferation, and cellular homeostasis were evaluated. Alachlor arrested cell cycle progression by blocking the expression of cyclin and cyclin-dependent kinases, and induced the breakdown of Ca2+ homeostasis. The cytosolic and mitochondrial levels of Ca2+ were also abnormally increased after the treatment of cells with alachlor, ultimately leading to the depolarization of mitochondrial membrane potential in MAC-T cells. The signaling cascade was found to be dysregulated by the abnormal phosphorylation of signaling molecules involved in PI3K/AKT (AKT, p70S6K, and S6) and MAPK/JNK (JNK and c-Jun) pathways. In these mechanisms, exposure to alachlor led to a reduction in the viability and proliferation of MAC-T cells. Altogether, the toxic effects of alachlor can lead to abnormal conditions in epithelial cells of the bovine mammary gland, which might hinder these cells from performing their main role, such as producing milk.

Original languageEnglish
Article number105063
JournalPesticide Biochemistry and Physiology
DOIs
Publication statusAccepted/In press - 2022

Keywords

  • Alachlor
  • Calcium homeostasis
  • Cell cycle
  • Mammary gland epithelial cell
  • Proliferation

ASJC Scopus subject areas

  • Agronomy and Crop Science
  • Health, Toxicology and Mutagenesis

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