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

So Ra Jeong, Kwang Won Lee

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number6530
JournalInternational journal of molecular sciences
Volume22
Issue number12
DOIs
Publication statusPublished - 2021 Jun 2

Keywords

  • Endoplasmic reticulum stress
  • JNK signal pathway
  • Kidney injury
  • Methylglyoxal-derived AGEs
  • Mitochondrial dysfunction

ASJC Scopus subject areas

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

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