Metformin alleviates oxidative stress-induced senescence of human lens epithelial cells via AMPK activation and autophagic flux restoration.
Metformin alleviates oxidative stress-induced senescence of human lens epithelial cells via AMPK activation and autophagic flux restoration.
复制标题
二甲双胍通过 AMPK 激活和自噬通量恢复减轻氧化应激诱导的人晶状体上皮细胞衰老
DOI：
10.1111/jcmm.16797
复制
发表时间：
2021-09
影响因子：
5.3
通讯作者：
Qi Y
中科院分区：
文献类型：
--
作者：
Chen M;Zhang C;Zhou N;Wang X;Su D;Qi Y
白内障是世界范围内失明的主要原因，这是由于老年人在人口中的比例不断增加。本研究的目的是探讨二甲双胍是否可以减轻年龄相关性白内障（ARC）的发生和发展及其机制。在本研究中，我们建立了氧化应激诱导的衰老模型，通过测定β-半乳糖苷酶活性、qRT-PCR和Western blotting证实了这一点。此外，我们发现二甲双胍通过激活AMPK缓解了氧化应激诱导的HLE‐B3细胞衰老。接下来，我们提供了氧化应激损害自噬通量和诱导溶酶体功能障碍的证据。随后，我们发现二甲双胍通过激活AMPK恢复了氧化应激损伤的自噬通量。此外，我们发现二甲双胍通过改善溶酶体功能和灭活mTOR来抑制HLE-B3细胞衰老。此外，在ARC的人透镜上皮中观察到AMPK失活、自噬通量受损和溶酶体功能障碍。总之，我们的数据表明，AMPK的激活可能是预防ARC的潜在策略，二甲双胍可能是缓解ARC形成和发展的新兴候选药物。
Cataracts are the leading cause of blindness worldwide owing to the increasing proportion of elderly individuals in the population. The purpose of this study was to investigate whether metformin could alleviate the occurrence and development of age‐related cataract (ARC) and the underlying mechanism. In the present study, we established a senescence model induced by oxidative stress, which was confirmed by measuring β‐galactosidase activity, qRT‐PCR and Western blotting. In addition, we showed that metformin alleviated the oxidative stress‐induced senescence of HLE‐B3 cells via the activation of AMPK. Next, we provided evidence that oxidative stress impaired autophagic flux and induced lysosomal dysfunction. Subsequently, we found that metformin restored autophagic flux that had been impaired by oxidative stress by activating AMPK. Additionally, we found that metformin suppressed HLE‐B3 cell senescence by improving lysosomal function and inactivating mTOR. Furthermore, the inactivation of AMPK, impairment of autophagic flux and lysosomal dysfunction were observed in the human lens epithelium of ARC. In summary, our data suggest that the activation of AMPK may be a potential strategy for preventing ARC, and metformin may be an emerging candidate to alleviate the formation and development of ARC.
登录
查看更多内容
影响因子：
13.7
作者：
Chang JR;Koo E;Agrón E;Hallak J;Clemons T;Azar D;Sperduto RD;Ferris FL 3rd;Chew EY;Age-Related Eye Disease Study Group
通讯作者：
Age-Related Eye Disease Study Group
衰老晶状体上皮细胞对人类年龄相关性皮质白内障严重程度的影响：病例对照研究
影响因子：
1.6
作者：
Fu, Qiuli;Qin, Zhenwei;Yao, Ke
通讯作者：
Yao, Ke
影响因子：
158.5
作者：
Holman, Rury R.;Paul, Sanjoy K.;Neil, H. Andrew W.
通讯作者：
Neil, H. Andrew W.
DOI：
10.1016/j.bbrc.2016.11.139
发表时间：
2017-01-22
影响因子：
3.1
作者：
Rwei, Patrick;Gong, Cihun-Siyong Alex;Liu, Hao-Li
通讯作者：
Liu, Hao-Li
DOI：
10.1016/j.bbadis.2018.01.018
发表时间：
2018-04-01
影响因子：
6.2
作者：
Karnewar, Santosh;Neeli, Praveen Kumar;Kotamraju, Srigiridhar
通讯作者：
Kotamraju, Srigiridhar