Cyclosporin A protects JEG-3 cells against oxidative stress-induced apoptosis by inhibiting the p53 and JNK/p38 signalin
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(2020) 18:100
RESEARCH
Open Access
Cyclosporin A protects JEG-3 cells against oxidative stress-induced apoptosis by inhibiting the p53 and JNK/p38 signaling pathways Bin He1†, Qi Yue Li1†, Yuan Yuan Wu1, Jing Ling Ruan1, Xiao Ming Teng1, Da Jin Li2 and Chuan Ling Tang1*
Abstract Background: Trophoblast cells are required for the establishment of pregnancy and fetal development. Apoptosis is an essential feature for trophoblast invasion. Uncontrolled trophoblast apoptosis is related to some complicate pregnancies. Oxidative stress (OS) is an important inducer of trophoblast apoptosis. Cyclosporin A (CsA) has been shown to promote the activity of trophoblast cells and reduce OS-induced oxidative injury. We investigated the role and mechanism of CsA in oxidative stress-induced trophoblast cell apoptosis. Methods: JEG-3 cells were cocultured with H2O2 and CsA. Cell viability and morphology were measured by MTT assay and DAPI staining. Cell apoptosis was tested with annexin V/PI staining. The expression of Bcl-2-associated X protein (Bax), B-cell lymphoma/leukemia-2 (Bcl-2), cleaved poly (ADP-ribose) polymerase (PARP) and pro-caspase-3 was assayed by western blotting. The protein expression and phosphorylation of p53 and mitogen-activated protein kinase (MAPK) kinases (JNK, ERK1/2 and p38) were examined by western blotting. Results: CsA increased the viability, alleviated morphological injury and reduced cell apoptosis of the H2O2-treated JEG-3 cells. CsA also attenuated the activation of p53, decreased the expression of Bax and cleavage of PARP, and increased the expression of Bcl-2 and pro-caspase-3 in the JEG-3 treated with H2O2. Furthermore, CsA reduced the activation of JNK and P38 but had no significant effect on the activation of extracellular signal-regulated kinase 1/2 (ERK1/2) in the H2O2-treated JEG-3 cells. Promoting the activation of JNK and p38 impaired the protective effect of CsA on OS-induced trophoblast apoptosis. Conclusions: These results suggested that CsA protected trophoblast cells from OS-induced apoptosis via the inhibition of the p53 and JNK/p38 signaling pathways. Keywords: Apoptosis, Oxidative stress, Trophoblast, p53, MAPK
* Correspondence: [email protected] † Bin He and Qi Yue Li contributed equally to this work. 1 Department of Reproductive Medicine, Shanghai First Maternity and Infant Hospital, Tongji University School of Medicine, Shanghai 201204, China Full list of author information is available at the end of the article © The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material
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