Purple sweet potato color attenuated NLRP3 inflammasome by inducing autophagy to delay endothelial senescence
Purple sweet potato color attenuated NLRP3 inflammasome by inducing autophagy to delay endothelial senescence
复制标题
紫甘薯颜色通过诱导自噬来减弱 NLRP3 炎症小体，从而延缓内皮衰老。
DOI：
10.1002/jcp.28003
复制
发表时间：
2019-05-01
影响因子：
5.6
通讯作者：
Zheng, Yuanlin
中科院分区：
文献类型：
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作者：
Sun, Chunhui;Diao, Qiaoqiao;Zheng, Yuanlin
自噬是调节细胞衰老的重要负性因素。紫甘薯色素（PSPC）是一种黄酮类化合物，通过抑制NLRP 3炎性小体的核苷酸结合寡聚化结构域、富含亮氨酸重复序列和吡啉结构域，具有抑制糖尿病小鼠血管内皮细胞衰老和恢复血管内皮功能的作用。然而，自噬在内皮衰老过程中的炎症反应中的作用尚不清楚。在这里，我们发现PSPC增强自噬以限制高糖诱导的内皮过早衰老。此外，PSPC给药通过增加自噬损害糖尿病小鼠的内皮衰老。自噬的抑制加速内皮细胞衰老，而自噬的增强延迟衰老。此外，由PSPC触发的NLRP 3炎性体的失活是自噬依赖性的。自噬受体微管相关蛋白1轻链3和p62与炎性体组分NLRP 3相互作用，表明自噬体靶向NLRP 3炎性体并将其递送至溶酶体进行降解。总之，PSPC放大细胞自噬，随后减弱NLRP 3炎性体活性，最终延迟内皮衰老以改善心血管并发症。这些结果提示了衰老相关心血管疾病的潜在治疗靶点。
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.