Advanced Oxidative Protein Products Drive Trophoblast Cells Into Senescence by Inhibiting the Autophagy: The Potential Implication of Preeclampsia

Li，Zhengjuan1,2; Wang，Shuoshi1; Li，Liping1

2022-03-09

10.3389/fcell.2022.810282

Frontiers in Cell and Developmental Biology   影响因子和分区

2296-634X

2296-634X

Introduction: Advanced oxidation protein products (AOPPs), the novel marker of oxidative stress, have been found to be elevated in preeclampsia (PE). To date, the effect of AOPPs on the senescence of trophoblast cells is still unclear. In this study, we investigated whether AOPPs promoted the senescence of trophoblast cells and explored the underlying mechanisms of AOPPs-induced aging process which may facilitate the progression of PE. Methods: The trophoblast cell line HTR-8/SV neo cells were cultured in the presence of PBS, AOPPs, AOPPs plus an anti-oxidant N-acetyl-L-cysteine (NAC). In some experiments, cells were pre-treated with rapamycin (an activator of autophagy), 3-MA (an inhibitor of autophagy), or cyclic pifithrin-α (PFT-α, an antagonist of p53), and then treated with AOPPs. Cellular senescence was analyzed by measuring the levels of senescence-associated β-galactosidase (SA β-Gal), senescence-associated heterochromatin foci (SAHF), mitochondrial membrane potential (ΔΨm), and cell cycle. Cell autophagic flux was analyzed by measuring tandem fluorescence-tagged LC3 reporter (mCherry-EGFP-LC3). Levels of p53, phosphorylated p53 (p-p53), p21, BECN1, p62, p-mTOR and p-p70S6K were measured by western blot. Results: Treatment with AOPPs significantly increased the levels of SA β-Gal and SAHF, the percentage of cells in the G0/G1 phase, and decreased cell ΔΨm compared with the control group. Co-treatment with NAC and AOPPs significantly reversed AOPPs-induced senescence. Pre-treatment with rapamycin or 3-MA significantly inhibited or promoted AOPPs-induced senescence, respectively. In addition, administration of AOPPs significantly decreased the numbers of mCherryEGFP autophagosomes and mCherryEGFP autolysosomes in cells compared with cells treated with PBS. Furthermore, AOPPs significantly increased the levels of proteins p-p53, p21, p-mTOR and p-p70S6K compared with the control group. Pre-treatment with rapamycin or PFT-α significantly down-regulated the levels of SA β-Gal, SAHF, p-p53, p21, autophagy related protein p62, the percentage of cells in the G0/G1 phase, and significantly up-regulated ΔΨm, autophagy related protein BECN1, autophagosomes and autolysosomes compared with cells only treated with AOPPs. Conclusion: AOPPs may induce trophoblast cell senescence by inhibiting the autophagy process in a p53/mTOR/p70S6K-dependent pathway.

AOPPs autophagy mTOR oxidative Stress p53 preeclampsia senescence trophoblast cells

SCI

英语

第一 ; 通讯

National Natural Science Foundation of China[81871217] ; Guangdong Natural Science Foundation Youth Project[2020A1515110024]

Cell Biology ; Developmental Biology

Cell Biology ; Developmental Biology

WOS:000776459200001

FRONTIERS MEDIA SA

2-s2.0-85127367319

Scopus

1.Department of Obstetrics,Shenzhen People’s Hospital,The Second Clinical Medical College,Jinan University,The First Affiliated Hospital,Southern University of Science and Technology),Shenzhen,China
2.Department of Obstetrics and Gynecology,The Second Affiliated Hospital,School of Medicine,South China University of Technology,Guangzhou,China

Li，Zhengjuan,Wang，Shuoshi,Li，Liping. Advanced Oxidative Protein Products Drive Trophoblast Cells Into Senescence by Inhibiting the Autophagy: The Potential Implication of Preeclampsia[J]. Frontiers in Cell and Developmental Biology,2022,10.

Li，Zhengjuan,Wang，Shuoshi,&Li，Liping.(2022).Advanced Oxidative Protein Products Drive Trophoblast Cells Into Senescence by Inhibiting the Autophagy: The Potential Implication of Preeclampsia.Frontiers in Cell and Developmental Biology,10.

Li，Zhengjuan,et al."Advanced Oxidative Protein Products Drive Trophoblast Cells Into Senescence by Inhibiting the Autophagy: The Potential Implication of Preeclampsia".Frontiers in Cell and Developmental Biology 10(2022).