Expression of Clusterin suppresses Cr(VI)-induced premature senescence through activation of PI3K/AKT pathway

Ecotoxicology and Environmental Safety
Yujing ZhangFang Xiao

Abstract

Our group found that long-term low-dose exposure to hexavalent chromium [Cr(VI)] in L-02 hepatocytes resulted in premature senescence, which accompanied by the increased expression of Clusterin (CLU), but the functional role of CLU in premature senescence has never been explored. In the present study, the CLU overexpressed or silenced L-02 hepatocytes were established by lentiviral vector transfection. Cell viability assay, cell cycle analysis, western blotting, plate clone formation assay, and confocal microcopy were performed. The results indicated that Cr(VI)-induced premature senescence was associated with phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT) pathway inhibition, and high expression of CLU in the senescent cells exerted its functional role of promoting cell proliferation. CLU could complex with eukaryotic translation initiation factor 3 subunit I (EIF3I) and prevent its degradation, leading to the increase of AKT activity in Cr(VI)-exposed senescent hepatocytes. Blockage of the PI3K/AKT pathway with its inhibitor LY294002 eliminated the inhibitory effect of CLU on Cr(VI)-induced premature senescence. We concluded that high expression of CLU suppressed Cr(VI)-induced premature senescence through activat...Continue Reading

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Citations

Feb 20, 2020·Combinatorial Chemistry & High Throughput Screening·Esra CakirIsil O Turan
Feb 6, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Zizhen SiXidi Wang
Nov 13, 2020·Toxicology Research·Yuehui LiangFang Xiao
Mar 25, 2021·Environmental Toxicology and Pharmacology·Yiran ZhuJianzhu Liu

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