PADI4 介导自噬，并通过 Akt/mTOR 通路参与灵芝酸 A 单体延缓阿尔茨海默病细胞衰老的作用。

PADI4 mediates autophagy and participates in the role of ganoderic acid A monomers in delaying the senescence of Alzheimer's cells through the Akt/mTOR pathway.

机构信息

Disease Prevention and Health Management Center, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, China.

Disease Prevention and Health Management Center, People's Hospital of Songyang, Lishui, Zhejiang Province, China.

出版信息

Biosci Biotechnol Biochem. 2021 Jul 23;85(8):1818-1829. doi: 10.1093/bbb/zbab054.

DOI:10.1093/bbb/zbab054

PMID:33963744

Abstract

The effects of PADI4 and GAA on the senescence of Alzheimer's cells were explored in the present work. HT22 cells were treated with Aβ25-35 to establish an Alzheimer's model and were then treated with different concentrations of GAA and transfected with a siPADI4 lentiviral vector. GAA could reverse the effects of Aβ25-35 on inhibiting cell viability and promoting apoptosis and senescence. siPADI4 reduced Aβ25-35-induced cell viability and upregulated Aβ25-35-induced cell apoptosis and senescence, as well as partially reversed the effect of GAA on cells, and these results were confirmed by detecting the expressions of senescence- and apoptosis-related proteins. In addition, siPADI4 was found to promote the phosphorylation of Akt and mTOR, which was partially reversed by GAA. In conclusion, PADI4 mediates autophagy and participates in the role of GAA monomers in delaying the senescence of Alzheimer's cells through the Akt/mTOR pathway.

摘要

本研究探讨了 PADI4 和 GAA 对阿尔茨海默病细胞衰老的影响。用 Aβ25-35 处理 HT22 细胞以建立阿尔茨海默病模型，然后用不同浓度的 GAA 和转染 siPADI4 慢病毒载体进行处理。GAA 可逆转 Aβ25-35 抑制细胞活力、促进细胞凋亡和衰老的作用。siPADI4 降低了 Aβ25-35 诱导的细胞活力，上调了 Aβ25-35 诱导的细胞凋亡和衰老，并部分逆转了 GAA 对细胞的作用，这些结果通过检测与衰老和凋亡相关的蛋白表达得到了证实。此外，发现 siPADI4 促进了 Akt 和 mTOR 的磷酸化，而 GAA 部分逆转了这一作用。总之，PADI4 通过 Akt/mTOR 通路介导自噬，并通过 GAA 单体参与延缓阿尔茨海默病细胞衰老的作用。