Selective activation of endoplasmic reticulum stress by reactive-oxygen-species-mediated ochratoxin a-induced apoptosis in tubular epithelial cells

Chong Sun Khoi; Yu Wen Lin; Jia Huang Chen; Biing Hui Liu; Tzu Yu Lin; Kuan Yu Hung; Chih Kang Chiang

doi:10.3390/ijms222010951

Selective activation of endoplasmic reticulum stress by reactive-oxygen-species-mediated ochratoxin a-induced apoptosis in tubular epithelial cells

Chong Sun Khoi, Yu Wen Lin, Jia Huang Chen, Biing Hui Liu, Tzu Yu Lin, Kuan Yu Hung, Chih Kang Chiang

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Ochratoxin A (OTA), one of the major food-borne mycotoxins, impacts the health of humans and livestock by contaminating food and feed. However, the underlying mechanism of OTA nephrotoxicity remains unknown. This study demonstrated that OTA induced apoptosis through selective endoplasmic reticulum (ER) stress activation in human renal proximal tubular cells (HK-2). OTA increased ER-stress-related JNK and precursor caspase-4 cleavage apoptotic pathways. Further study revealed that OTA increased reactive oxygen species (ROS) levels, and N-acetyl cysteine (NAC) could reduce OTA-induced JNK-related apoptosis and ROS levels in HK-2 cells. Our results demonstrate that OTA induced ER stress-related apoptosis through an ROS-mediated pathway. This study provides new evidence to clarify the mechanism of OTA-induced nephrotoxicity.

Original language	English
Article number	10951
Journal	International journal of molecular sciences
Volume	22
Issue number	20
DOIs	https://doi.org/10.3390/ijms222010951
Publication status	Published - Oct 1 2021
Externally published	Yes

Keywords

Apoptosis
ER stress
HK-2 cell
Ochratoxin A
Reactive oxygen species

ASJC Scopus subject areas

Catalysis
Molecular Biology
Spectroscopy
Computer Science Applications
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/ijms222010951

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title = "Selective activation of endoplasmic reticulum stress by reactive-oxygen-species-mediated ochratoxin a-induced apoptosis in tubular epithelial cells",

abstract = "Ochratoxin A (OTA), one of the major food-borne mycotoxins, impacts the health of humans and livestock by contaminating food and feed. However, the underlying mechanism of OTA nephrotoxicity remains unknown. This study demonstrated that OTA induced apoptosis through selective endoplasmic reticulum (ER) stress activation in human renal proximal tubular cells (HK-2). OTA increased ER-stress-related JNK and precursor caspase-4 cleavage apoptotic pathways. Further study revealed that OTA increased reactive oxygen species (ROS) levels, and N-acetyl cysteine (NAC) could reduce OTA-induced JNK-related apoptosis and ROS levels in HK-2 cells. Our results demonstrate that OTA induced ER stress-related apoptosis through an ROS-mediated pathway. This study provides new evidence to clarify the mechanism of OTA-induced nephrotoxicity.",

keywords = "Apoptosis, ER stress, HK-2 cell, Ochratoxin A, Reactive oxygen species",

author = "Khoi, {Chong Sun} and Lin, {Yu Wen} and Chen, {Jia Huang} and Liu, {Biing Hui} and Lin, {Tzu Yu} and Hung, {Kuan Yu} and Chiang, {Chih Kang}",

note = "Funding Information: Funding: This work was supported by grants from National Taiwan University Hospital (NTUH-108-S4373, NTUH-UN-109-S4785, NTUH-110-S5074) and the NTUH-FEMH Joint research program (108-FTN16). Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

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doi = "10.3390/ijms222010951",

language = "English",

volume = "22",

journal = "International journal of molecular sciences",

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TY - JOUR

T1 - Selective activation of endoplasmic reticulum stress by reactive-oxygen-species-mediated ochratoxin a-induced apoptosis in tubular epithelial cells

AU - Khoi, Chong Sun

AU - Lin, Yu Wen

AU - Chen, Jia Huang

AU - Liu, Biing Hui

AU - Lin, Tzu Yu

AU - Hung, Kuan Yu

AU - Chiang, Chih Kang

N1 - Funding Information: Funding: This work was supported by grants from National Taiwan University Hospital (NTUH-108-S4373, NTUH-UN-109-S4785, NTUH-110-S5074) and the NTUH-FEMH Joint research program (108-FTN16). Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021/10/1

Y1 - 2021/10/1

N2 - Ochratoxin A (OTA), one of the major food-borne mycotoxins, impacts the health of humans and livestock by contaminating food and feed. However, the underlying mechanism of OTA nephrotoxicity remains unknown. This study demonstrated that OTA induced apoptosis through selective endoplasmic reticulum (ER) stress activation in human renal proximal tubular cells (HK-2). OTA increased ER-stress-related JNK and precursor caspase-4 cleavage apoptotic pathways. Further study revealed that OTA increased reactive oxygen species (ROS) levels, and N-acetyl cysteine (NAC) could reduce OTA-induced JNK-related apoptosis and ROS levels in HK-2 cells. Our results demonstrate that OTA induced ER stress-related apoptosis through an ROS-mediated pathway. This study provides new evidence to clarify the mechanism of OTA-induced nephrotoxicity.

AB - Ochratoxin A (OTA), one of the major food-borne mycotoxins, impacts the health of humans and livestock by contaminating food and feed. However, the underlying mechanism of OTA nephrotoxicity remains unknown. This study demonstrated that OTA induced apoptosis through selective endoplasmic reticulum (ER) stress activation in human renal proximal tubular cells (HK-2). OTA increased ER-stress-related JNK and precursor caspase-4 cleavage apoptotic pathways. Further study revealed that OTA increased reactive oxygen species (ROS) levels, and N-acetyl cysteine (NAC) could reduce OTA-induced JNK-related apoptosis and ROS levels in HK-2 cells. Our results demonstrate that OTA induced ER stress-related apoptosis through an ROS-mediated pathway. This study provides new evidence to clarify the mechanism of OTA-induced nephrotoxicity.

KW - Apoptosis

KW - ER stress

KW - HK-2 cell

KW - Ochratoxin A

KW - Reactive oxygen species

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Selective activation of endoplasmic reticulum stress by reactive-oxygen-species-mediated ochratoxin a-induced apoptosis in tubular epithelial cells

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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