Proteomic Investigation of Glyceraldehyde-Derived Intracellular AGEs and Their Potential Influence on Pancreatic Ductal Cells

Authors

Lakmini Senavirathna
Cheng Ma
Ru Chen
Sheng Pan

Publication Date

4-24-2021

Journal

Cells

DOI

10.3390/cells10051005

PMID

33923186

PMCID

PMC8145644

PubMedCentral® Posted Date

4-24-2021

PubMedCentral® Full Text Version

Post-Print

Published Open-Access

yes

Keywords

Apoptosis, Biomarkers, Tumor, Carcinoma, Pancreatic Ductal, Cell Survival, Glycation End Products, Advanced, Glyceraldehyde, Glycosylation, Humans, Oxidative Stress, Pancreatic Neoplasms, Proteome, Tumor Cells, Cultured, glycation, advanced glycation end products (AGEs), pancreatic cancer, glyceraldehyde, proteomics, mass spectrometry

Abstract

Glyceraldehyde-derived advanced glycation end products (AGEs) play an important role in the pathogenesis of many diseases including cancer. Accumulation of intracellular AGEs could stimulate cancer induction and facilitate cancer progression. We evaluated the toxic effect of glyceraldehyde-derived intracellular AGEs on normal and malignant pancreatic ductal cells by assessing the cell viability, toxicity, and oxidative stress, followed by proteomic analysis. Our functional studies showed that pancreatic cancer cells (PANC-1 and MIA PaCa-2) were more resistant to glyceraldehyde treatment compared to normal pancreatic ductal epithelial cells (HPDE), while cytotoxicity effects were observed in all cell types. Furthermore, using 13C isotopic labeled glyceraldehyde, the proteomic data revealed a dose-dependent increment of the number of glycation adducts in both these cell types. HPDE cells showed a higher number of intracellular AGEs compared to cancer cells. At a molecular level, the glycations in the lysine residues of proteins showed a concurrent increase with the concentration of the glyceraldehyde treatment, while the arginine glycations appeared to be less affected by the glyceraldehyde doses. Further pathway analysis of these glycated proteins suggested that the glycated proteins participate in important biological processes that are major hallmarks of cancer initiation and progression, including metabolic processes, immune response, oxidative stress, apoptosis, and S100 protein binding.

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