自噬
安普克
衰老
细胞生物学
PI3K/AKT/mTOR通路
活性氧
蛋白激酶A
氧化应激
AMP活化蛋白激酶
信号转导
激酶
生物
化学
生物化学
细胞凋亡
作者
Xiang‐Yu Zhao,Shaojun Zhou,Shunmei Huang,Peixia Wang,Jie Mou,Caixia Gong,Zhengyuan Xia,Qin Zhang,Yongxue Yang
标识
DOI:10.1089/rej.2022.0061
摘要
Intestinal epithelial cellular senescence contributes to the physiological decline of intestine and induces age-associated intestinal diseases. Therefore, the intestine is a vital target to delay intestinal epithelial cellular senescence and extend healthy lifespan. Alginate oligosaccharides (AOSs) have a wide range of biological and pharmacological activities. However, there are no related reports of AOSs on intestinal epithelial cellular senescence. Our study aimed to investigate the effect of AOSs on hydrogen peroxide (H2O2)-induced senescent intestinal epithelial cells (IEC-6) and its antiaging mechanism. A senescent model was successfully constructed by H2O2 (200 μmol/L) treatment on IEC-6 for 4 hours. Different concentrations of AOSs (10, 50, 100 μg/mL) were used to intervene in H2O2-induced senescent IEC-6. The number of β-galactosidase staining-positive cells was significantly reduced by AOS intervention. The expression levels of p21 and p16, known as the senescent biomarkers, were also decreased. In addition, AOSs alleviated oxidative stress by reducing reactive oxygen species and improving antioxidative ability. To understand how AOSs rejuvenate H2O2-induced senescent IEC-6, we detected the expression level of genes in autophagy process. The results indicated that AOSs restored the expression level of Beclin 1, Atg7, and LC3 to enhance autophagy process by activating activated protein kinase (AMPK) and inhibiting mammalian target of rapamycin in H2O2-induced senescent IEC-6. Compound C, an AMPK inhibitor, abolished the effect of AOSs on activating autophagy and rejuvenating senescent IEC-6. Altogether, our study suggests that AOS is a promising drug for delaying intestinal epithelial cellular senescence.
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