Cyclosporin A protects JEG-3 cells against oxidative stress-induced apoptosis by inhibiting the p53 and JNK/p38 signaling pathways

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.

Tocopherol attenuates the oxidative stress of BMSCs by inhibiting ferroptosis through the PI3k/AKT/mTOR pathway

“…For example, emodin could protect the hepatocyte cell line from paracetamol-induced oxidative damage by the activation of the AMPK pathway ( Lee et al, 2020 ). Cyclosporin A had been shown to increase the viability of trophoblast cells and reduce the ROS-induced oxidative injury by the inhibition of the p38 pathway ( He et al, 2020 ). Overexpression of Parkinson’s disease protein 7 prevented the oxidative stress-induced apoptosis of transplanted BMSCs by the activation of the ERK1/2 pathway ( Zhang et al, 2021 ).…”

Oral immunosuppressants improve pregnancy outcomes in women with idiopathic recurrent miscarriage: A meta‐analysis

“…Meanwhile, studies have found that lowdose CsA can promote the proliferation, invasion, and migration of trophoblast cells in early pregnancy by activating the MAPK signaling pathway. 33,34 In addition, animal studies have also confirmed that low-dose CsA can improve the pregnancy outcomes of abortive model mice by promoting the proliferation and invasion of trophoblast cells in mice and inducing immune tolerance. 35 Studies have also Prednisolone is a type of glucocorticoid that can inhibit the generation and release of histamine and other inflammatory mediators and has a strong immunosuppressive effect.…”

“…In recent years, many studies have found that CsA has a bidirectional regulatory effect on the maternal–fetal interface. Meanwhile, studies have found that low‐dose CsA can promote the proliferation, invasion, and migration of trophoblast cells in early pregnancy by activating the MAPK signaling pathway 33,34 . In addition, animal studies have also confirmed that low‐dose CsA can improve the pregnancy outcomes of abortive model mice by promoting the proliferation and invasion of trophoblast cells in mice and inducing immune tolerance 35 .…”

Characterization of Xenobiotic and Steroid Disposition Potential of Human Placental Tissue and Cell Lines (BeWo, JEG-3, JAR, and HTR-8/SVneo) by Quantitative Proteomics

“…BeWo cells have been utilized to study ABCG2 (BCRP) efflux (Crowe and Keelan, 2012) and JEG-3 cells have been utilized to study the functions of CYP19A1 and HSDs (Liu et al, 2016). Similarly, JEG-3 cells have recently been utilized in multiple studies focused on endocrine disruption due to xenobiotic exposure which includes exposures to alkylphenols (Pérez-Albaladejo et al, 2019), phthalates (Zhang et al, 2020), bisphenol A (Xu et al, 2019), acetaminophen (Addo et al, 2021), and cyclosporin A (He et al, 2020). Further, JEG-3 cells have been used in several studies and are regarded as a promising tool in placental toxicological studies (Olivier et al, 2021).…”