TY - JOUR
T1 - Methylglyoxal-derived advanced glycation end product (Age4)-induced apoptosis leads to mitochondrial dysfunction and endoplasmic reticulum stress through the rage/jnk pathway in kidney cells
AU - Jeong, So Ra
AU - Lee, Kwang Won
N1 - Funding Information:
This research was funded by the Korea Food Research Institute, grant number E0164400-04 and Korea University, grant number K1516071. The authors thank School of Life Sciences & Biotechnology of Korea University (BK21PLUS) and the Institute of Biomedical Science & Food Safety, CJ-Korea University Food Safety Hall (Seoul, Republic of Korea) for providing the equipment and facilities.
Funding Information:
Funding: This research was funded by the Korea Food Research Institute, grant number E0164400-04 and Korea University, grant number K1516071. The authors thank School of Life Sciences & Biotechnology of Korea University (BK21PLUS) and the Institute of Biomedical Science & Food Safety, CJ-Korea University Food Safety Hall (Seoul, Republic of Korea) for providing the equipment and facilities.
Publisher Copyright:
© 2021 by the authorsLicensee MDPI, Basel, Switzerland.
PY - 2021/6/2
Y1 - 2021/6/2
N2 - Advanced glycation end products (AGEs) are formed via nonenzymatic reactions between reducing sugars and proteins. Recent studies have shown that methylglyoxal, a potent precursor for AGEs, causes a variety of biological dysfunctions, including diabetes, inflammation, renal failure, and cancer. However, little is known about the function of methylglyoxal-derived AGEs (AGE4) in kidney cells. Therefore, we verified the expression of endoplasmic reticulum (ER) stress-related genes and apoptosis markers to determine the effects of AGE4 on human proximal epithelial cells (HK-2). Moreover, our results showed that AGE4 induced the expression of apoptosis markers, such as Bax, p53, and kidney injury molecule-1, but downregulated Bcl-2 and cyclin D1 levels. AGE4 also promoted the expression of NF-κB, serving as a transcription factor, and the phosphorylation of c-Jun NH2-terminal kinase (JNK), which induced cell apoptosis and ER stress mediated by the JNK inhibitor. Furthermore, AGE4 induced mitochondrial dysfunction by inducing the permeabilization of the mitochondrial membrane and ATP synthesis. Through in vitro and in vivo experiments, this study provides a new perspective on renal dysfunction with regard to the AGE4-induced RAGE /JNK signaling pathway, which leads to renal cell apoptosis via the imbalance of mitochondrial function and ER stress in kidney damage.
AB - Advanced glycation end products (AGEs) are formed via nonenzymatic reactions between reducing sugars and proteins. Recent studies have shown that methylglyoxal, a potent precursor for AGEs, causes a variety of biological dysfunctions, including diabetes, inflammation, renal failure, and cancer. However, little is known about the function of methylglyoxal-derived AGEs (AGE4) in kidney cells. Therefore, we verified the expression of endoplasmic reticulum (ER) stress-related genes and apoptosis markers to determine the effects of AGE4 on human proximal epithelial cells (HK-2). Moreover, our results showed that AGE4 induced the expression of apoptosis markers, such as Bax, p53, and kidney injury molecule-1, but downregulated Bcl-2 and cyclin D1 levels. AGE4 also promoted the expression of NF-κB, serving as a transcription factor, and the phosphorylation of c-Jun NH2-terminal kinase (JNK), which induced cell apoptosis and ER stress mediated by the JNK inhibitor. Furthermore, AGE4 induced mitochondrial dysfunction by inducing the permeabilization of the mitochondrial membrane and ATP synthesis. Through in vitro and in vivo experiments, this study provides a new perspective on renal dysfunction with regard to the AGE4-induced RAGE /JNK signaling pathway, which leads to renal cell apoptosis via the imbalance of mitochondrial function and ER stress in kidney damage.
KW - Endoplasmic reticulum stress
KW - JNK signal pathway
KW - Kidney injury
KW - Methylglyoxal-derived AGEs
KW - Mitochondrial dysfunction
UR - http://www.scopus.com/inward/record.url?scp=85108114103&partnerID=8YFLogxK
U2 - 10.3390/ijms22126530
DO - 10.3390/ijms22126530
M3 - Article
C2 - 34207084
AN - SCOPUS:85108114103
SN - 1661-6596
VL - 22
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 12
M1 - 6530
ER -
