Ochratoxin A mediates cytotoxicity through the MAPK signaling pathway and alters intracellular homeostasis in bovine mammary epithelial cells. (March 2019)

• Record Type: Journal Article
• Authors: Lee, Jin-Young; Lim, Whasun; Ryu, Soomin; Kim, Jinyoung; Song, Gwonhwa
• Is Part Of: Environmental pollution. Volume 246(2019)
• Page Start: 366
• Page End: 373
• Publication Date: 2019-03
• Subjects: Ochratoxin A -- Mammary epithelial cell -- Cytotoxicity -- Contaminant -- Cow; Pollution -- Periodicals; Pollution -- Environmental aspects -- Periodicals; Environmental Pollution -- Periodicals; Pollution -- Périodiques; Pollution -- Aspect de l'environnement -- Périodiques; Pollution -- Effets physiologiques -- Périodiques; Pollution; Pollution -- Environmental aspects; Periodicals; Electronic journals; 363.73
• DOI: 10.1016/j.envpol.2018.12.032
• Languages: English
• ISSNs: 0269-7491

Abstract

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 Ca 2+ 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. Graphical abstract: Hypothetical schematic illustration of OTA induced apoptosis in bovine mammary epithelial cells. OTA induced apoptosis by activating JNK MAPK, P38 MAPK pathways, inducing DNA fragmentation and inhibition of cell cycle progression in bovine mammary epithelial cells. Furthermore, OTA decreased both cytosolic and mitochondrial Ca2+ concentration and disrupted MMP in a dose-dependent manner in MAC-T cells. Gene expression of occludin and claudin 3, as well as the composition of tight junction proteins, was decreased by OTA treatment in MAC-T cells. Moreover, OTA increased gene expression levels of inflammatory cytokines. Image 10942 Highlights: Ochratoxin A induces cell cycle arrest and apoptosis of mammary epithelial cells. Ochratoxin A results in mitochondrial membrane disruption of mammary epithelia. Ochratoxin A leads to a decrease in mitochondrial and cytosolic Ca 2+ in MAC-T cells. Ochratoxin A contamination may affect mammary functions of lactating cows.