Ochratoxin A mediates cytotoxicity through the MAPK signaling pathway and alters intracellular homeostasis in bovine mammary epithelial cells

Abstract

Ochratoxin A (OTA), a secondary metabolite of the genera Penicillium and Aspergillus, contaminates many types of food and causes apoptosis as well as immunosuppression in many animal species. However, a mechanistic analysis of OTA-mediated cytotoxicity in bovine mammary epithelial cells has not yet been performed. Hence, we investigated the effects of OTA on bovine mammary epithelial (MAC-T) cells using several mechanistic analyses. We report that OTA may induce cell cycle arrest and apoptosis via MAPK and JNK signaling pathways in MAC-T cells. Moreover, homeostasis of cellular components, such as that of the mitochondrial membrane, was disrupted by OTA, leading to a decrease in mitochondrial and cytosolic Ca2+ in MAC-T cells. In addition, we evaluated the effects of OTA on inflammatory responses and major tight junction regulators, such as occludin and claudin 3. In summation, we suggest that OTA contamination may adversely affect bovine mammary epithelial cells, leading to improper lactation and decreased milk quality. This article aims to improve the understanding of physiological mechanisms involved in lactation, in addition to providing a guideline for the stabilization of industrial milk production by countering exogenous contaminants in livestock.