TY - JOUR
T1 - Ochratoxin A mediates cytotoxicity through the MAPK signaling pathway and alters intracellular homeostasis in bovine mammary epithelial cells
AU - Lee, Jin Young
AU - Lim, Whasun
AU - Ryu, Soomin
AU - Kim, Jinyoung
AU - Song, Gwonhwa
N1 - Funding Information:
This research was supported by a grant of the Korea Health Technology R&D Project through the Korea Health Industry Development Institute funded by the Ministry of Health and Welfare (grant number: No. HI15C0810 awarded to G.S. and HI17C0929 awarded to W.L.)
Publisher Copyright:
© 2018 Elsevier Ltd
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
KW - Contaminant
KW - Cow
KW - Cytotoxicity
KW - Mammary epithelial cell
KW - Ochratoxin A
UR - http://www.scopus.com/inward/record.url?scp=85059306133&partnerID=8YFLogxK
U2 - 10.1016/j.envpol.2018.12.032
DO - 10.1016/j.envpol.2018.12.032
M3 - Article
C2 - 30577004
AN - SCOPUS:85059306133
VL - 246
SP - 366
EP - 373
JO - Environmental Pollution
JF - Environmental Pollution
SN - 0269-7491
ER -