Accumulation of Intracellular Protein Advanced Glycation End Products Alters Cellular Homeostasis for Protein Clearance in Pancreatic Ductal Epithelial Cells.
Biochemistry
; 63(14): 1723-1729, 2024 Jul 16.
Article
em En
| MEDLINE
| ID: mdl-38941592
ABSTRACT
Protein advanced glycation end products (AGEs) can be formed via nonenzymatic glycation and accumulated intracellularly to disrupt cellular homeostasis for protein clearance. Here, we investigated the formation particulars of intracellular protein AGEs and sought to elucidate the molecular events implicated in the impact of cellular clearance systems. The formation and accumulation of intracellular protein AGEs increased protein aggregation and protease resistance, potentially overwhelming the ubiquitin-proteasome system (UPS). At high levels of protein AGEs, the abundance of many E3 ligases decreased and the overall ubiquitination level was reduced, all of which indicated decreased UPS activity. On the other hand, autophagy activity was stimulated, as evidenced by the upregulation of autophagy marker LC3II and important proteins in autophagosome and autolysosome formation, as well as downregulation of mTOR. Understanding the functional impacts of intracellular protein AGEs on the UPS and autophagy could pave the way for the future development of pharmaceutical agents targeting AGE-related diseases.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Autofagia
/
Produtos Finais de Glicação Avançada
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Homeostase
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article