CLC number: R3
On-line Access: 2024-08-27
Received: 2023-10-17
Revision Accepted: 2024-05-08
Crosschecked: 2018-11-16
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Citations: Bibtex RefMan EndNote GB/T7714
Yu-chen Lin, Ze-ren Shen, Xiao-hui Song, Xin Liu, Ke Yao. Comparative transcriptomic analysis reveals adriamycin-induced apoptosis via p53 signaling pathway in retinal pigment epithelial cells[J]. Journal of Zhejiang University Science B, 2018, 19(12): 895-909.
@article{title="Comparative transcriptomic analysis reveals adriamycin-induced apoptosis via p53 signaling pathway in retinal pigment epithelial cells",
author="Yu-chen Lin, Ze-ren Shen, Xiao-hui Song, Xin Liu, Ke Yao",
journal="Journal of Zhejiang University Science B",
volume="19",
number="12",
pages="895-909",
year="2018",
publisher="Zhejiang University Press & Springer",
doi="10.1631/jzus.B1800408"
}
%0 Journal Article
%T Comparative transcriptomic analysis reveals adriamycin-induced apoptosis via p53 signaling pathway in retinal pigment epithelial cells
%A Yu-chen Lin
%A Ze-ren Shen
%A Xiao-hui Song
%A Xin Liu
%A Ke Yao
%J Journal of Zhejiang University SCIENCE B
%V 19
%N 12
%P 895-909
%@ 1673-1581
%D 2018
%I Zhejiang University Press & Springer
%DOI 10.1631/jzus.B1800408
TY - JOUR
T1 - Comparative transcriptomic analysis reveals adriamycin-induced apoptosis via p53 signaling pathway in retinal pigment epithelial cells
A1 - Yu-chen Lin
A1 - Ze-ren Shen
A1 - Xiao-hui Song
A1 - Xin Liu
A1 - Ke Yao
J0 - Journal of Zhejiang University Science B
VL - 19
IS - 12
SP - 895
EP - 909
%@ 1673-1581
Y1 - 2018
PB - Zhejiang University Press & Springer
ER -
DOI - 10.1631/jzus.B1800408
Abstract: Objective: This paper applied a transcriptomic approach to investigate the mechanisms of adriamycin (ADR) in treating proliferative vitreoretinopathy (PVR) using ARPE-19 cells. Methods: The growth inhibitory effects of ADR on ARPE-19 cells were assessed by sulforhodamine B (SRB) assay and propidium iodide (PI) staining using flow cytometry. The differentially expressed genes between ADR-treated ARPE-19 cells and normal ARPE-19 cells and the signaling pathways involved were investigated by microarray analysis. Mitochondrial function was detected by JC-1 staining using flow cytometry and the Bcl-2/Bax protein family. The phosphorylated histone H2AX (γ-H2AX), phosphorylated checkpoint kinase 1 (p-CHK1), and phosphorylated checkpoint kinase 2 (p-CHK2) were assessed to detect DNA damage and repair. Results: ADR could significantly inhibit ARPE-19 cell proliferation and induce caspase-dependent apoptosis in vitro. In total, 4479 differentially expressed genes were found, and gene ontology items and the p53 signaling pathway were enriched. A protein–protein interaction analysis indicated that the Tp53 protein molecules regulated by ADR were related to DNA damage and oxidative stress. ADR reduced mitochondrial membrane potential and the Bcl-2/Bax ratio. p53-knockdown restored the activation of c-caspase-3 activity induced by ADR by regulating Bax expression, and it inhibited ADR-induced ARPE-19 cell apoptosis. Finally, the levels of the γ-H2AX, p-CHK1, and p-CHK2 proteins were up-regulated after ADR exposure. Conclusions: The mechanism of ARPE-19 cell death induced by ADR may be caspase-dependent apoptosis, and it may be regulated by the p53-dependent mitochondrial dysfunction, activating the p53 signaling pathway through DNA damage.
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[46]List of electronic supplementary materials
[47]Fig. S1 Gene ontology (GO) enrichment analysis of all the differentially expressed genes
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