Dietary Nucleotides Retard Oxidative Stress-Induced Senescence of Human Umbilical Vein Endothelial Cells

• Published in: Nutrients 2021-09, Vol.13 (9), p.3279
• Main Authors: Zhu, Na, Liu, Xinran, Xu, Meihong, Li, Yong
• Format: Article
• Language: English
• Subjects: Antioxidants; Cardiovascular diseases; Cell adhesion & migration; Cell cycle; Cell proliferation; Cell viability; Cyclin-dependent kinase inhibitor p21; dietary nucleotides; Endothelial cells; Enzymatic activity; Enzyme activity; Flow cytometry; Galactosidase; HUVECs; Hydrogen peroxide; Inflammation; INK4a protein; Medical research; Membranes; Mitochondria; mitochondrial function; Morphology; Nucleotides; Oxidative stress; p16 Protein; Physiology; Proteins; Retarding; Senescence; Software; Umbilical vein; Variance analysis; β-Galactosidase
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu13093279

Several lines of evidence suggest an inhibitory role of dietary nucleotides (NTs) against oxidative stress and inflammation, which promote senescence in age-associated cardiovascular diseases. We sought to test whether the dietary NTs could retard the hydrogen peroxide (H2O2)-induced senescence of human umbilical vein endothelial cells (HUVECs) and to elucidate the efficiency of different NTs as well as the potential mechanism. Senescence was induced in HUVECs by 4 h exposure to 200 µM H2O2 and was confirmed using senescence-associated-β-galactosidase staining (SA-β-gal), cell viability, and Western blot analyses of p16INK4A and p21Waf1/Cip1 after 24 h administration of growth medium. We find that NTs retards oxidative stress-induced HUVECs senescence, as shown by a lower percentage of SA-β-gal-positive cells, lower expression of p16INK4A, and p21Waf1/Cip1 as well as higher cell viability. GMP100 was the most excellent in delaying HUVECs senescence, which was followed by the NTs mixture, NMN, CMP50, and UMP50/100, while AMP retards HUVECs senescence by specifically reducing p15INK4b expression. NTs all have significant anti-inflammatory effects; AMP and CMP were more prominent in restoring mitochondrial function, GMP and CMP were more competent at eliminating ROS and MDA, while AMP and UMP were more efficient at enhancing antioxidant enzyme activity. The role of the NTs mixture in retarding HUVECs senescence is full-scaled. These results stated that the mechanisms of NTs retarding HUVECs senescence could be related to its antioxidant and anti-inflammation properties promoting cell proliferation and protecting mitochondrial function activities.