Purple sweet potato color attenuated NLRP3 inflammasome by inducing autophagy to delay endothelial senescence

• Published in: Journal of cellular physiology Vol. 234; no. 5; pp. 5926 - 5939
• Main Authors: Sun, Chunhui, Diao, Qiaoqiao, Lu, Jun, Zhang, Zifeng, Wu, Dongmei, Wang, Xingqi, Xie, Jun, Zheng, Guihong, Shan, Qun, Fan, Shaohua, Hu, Bin, Zheng, Yuanlin
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01.05.2019
• Subjects: Aging; Animals; Anti-Inflammatory Agents - isolation & purification; Anti-Inflammatory Agents - pharmacology; Autophagosomes - drug effects; Autophagosomes - metabolism; Autophagy; Autophagy - drug effects; Autophagy-Related Proteins - metabolism; cardiovascular disease; Cardiovascular diseases; Cells, Cultured; Cellular Senescence - drug effects; Color; Cytokines - metabolism; Deactivation; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - metabolism; Diabetes Mellitus, Type 2 - pathology; Diet, High-Fat; Disease Models, Animal; endothelial cells; Endothelium; Flavonoids - isolation & purification; Flavonoids - pharmacology; Heart diseases; Human Umbilical Vein Endothelial Cells - drug effects; Human Umbilical Vein Endothelial Cells - metabolism; Human Umbilical Vein Endothelial Cells - pathology; Humans; Inflammasomes; Inflammation; Inflammatory response; Ipomoea batatas; Ipomoea batatas - chemistry; Leucine; Lysosomes - metabolism; Male; Mice; Mice, Inbred ICR; NLR Family, Pyrin Domain-Containing 3 Protein - metabolism; NLRP3 inflammasome; Oligomerization; Phagocytosis; Phagosomes; Pigments, Biological - isolation & purification; Pigments, Biological - pharmacology; Potatoes; Protein Denaturation; Protein Transport; Proteins; Pyrin protein; Recovery of function; Rodents; Senescence; Signal Transduction; Sweet potatoes; Therapeutic applications; senescence; cardiovascular disease; endothelial cells; autophagy; NLRP3 inflammasome
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.28003

Autophagy is a vital negative factor regulating cellular senescence. Purple sweet potato color (PSPC), one type of flavonoid, has been demonstrated to suppress endothelial senescence and restore endothelial function in diabetic mice by inhibiting the nucleotide‐binding oligomerization domain, leucine rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome. However, the roles of autophagy in the inflammatory response during endothelial senescence are unknown. Here, we found that PSPC augmented autophagy to restrict high‐glucose‐induced premature endothelial senescence. In addition, PSPC administration impaired endothelium aging in diabetic mice by increasing autophagy. Inhibition of autophagy accelerated endothelial senescence, while enhancement of autophagy delayed senescence. Moreover, deactivation of the NLRP3 inflammasome triggered by PSPC was autophagy‐dependent. Autophagy receptor microtubule‐associated protein 1 light chain 3 and p62 interacted with the inflammasome component NLRP3, suggesting that autophagosomes target the NLRP3 inflammasome and deliver it to the lysosome for degradation. Altogether, PSPC amplified cellular autophagy, subsequently attenuated NLRP3 inflammasome activity and finally delayed endothelial senescence to ameliorate cardiovascular complication. These results suggest a potential therapeutic target in senescence‐related cardiovascular diseases. Purple sweet potato color (PSPC) delays endothelial senescence by promoting autophagy. Autophagy receptor colocalizes with nucleotide‐binding oligomerization domain, leucine rich repeat and pyrin domain containing protein 3 (NLRP3) inflammasome. Autophagosomes induced by PSPC target the NLRP3 inflammasome and deliver it to the lysosome for degradation.