Effects of resveratrol on autophagy and the expression of inflammasomes in a placental trophoblast oxidative stress model

Li, Meihe; Wu, Xiaoling; An, Peng; Dang, Huimin; Yan-qiao, Liu; Liu, Runxia

doi:10.1016/j.lfs.2020.117890

Cited by 18 publications

(16 citation statements)

References 59 publications

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“…In our previous work, we found that the NLRP1 inflammasome was overexpressed in an oxidative stress model in placental trophoblast cells ( Li et al, 2020 ) and in the rat model of abortion that these could be used to investigate the presence of ferroptosis in an oxidative stress model. First, we used H 2 O 2 to establish a cell model of oxidative stress and then detected the expression levels of GPX4, a key protein involved in ferroptosis, by western blot.…”

Section: Resultsmentioning

confidence: 99%

“…The HTR-8/SVneo human trophoblast cell line applied in the present study is more similar to primary trophoblasts and normal human physiological conditions. In our previous work, we successfully established a model of oxidative stress in placental trophoblast cells ( Li et al, 2020 ). Cells were cultured in a 37°C, 5% CO 2 incubator plated on a six-well culture plate at a density of 1 × 10 5 cells per well.…”

Section: Methodsmentioning

confidence: 99%

“…Activation of the inflammasome requires the production of ROS because most known inflammasome stimuli trigger ROS production, and treatment with various ROS scavengers is known to prevent inflammasome responses to agonists ( Schweneker et al, 2013 ; Lebel et al, 2014 ). In our previous studies, we found that in H 2 O 2 -induced oxidative stress, there is a large amount of ROS production, as well as the overexpression of NLRP1 inflammasomes ( Li et al, 2020 ). This suggests that the NLRP1 inflammasome plays an important role in the occurrence and development of adverse pregnancy.…”

Section: Introductionmentioning

confidence: 99%

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The Ferroptosis-NLRP1 Inflammasome: The Vicious Cycle of an Adverse Pregnancy

Gao

Kang

et al. 2021

Front. Cell Dev. Biol.

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One of the hallmarks of placental dysfunction is the increase of oxidative stress. This process, along with the overexpression of the inflammasome, creates a downward spiral that can lead to a series of severe pregnancy complications. Ferroptosis is a form of iron-mediated cell death involving the accumulation of reactive oxygen species, lipid peroxides. In this study, the rats’ model of oxidative stress abortion was established, and hydrogen peroxide (H2O2) was used to establish a cellular model of placental oxidative stress. RNAi, western blot, and immunofluorescence were used to evaluate the expression of specific markers of ferroptosis and the expression of the inflammasome in placental trophoblast cells. We observed excessive levels of ferroptosis and inflammasome activation in both rats’ model and placental trophoblast cell model of oxidative stress. When the NLRP1 inflammasome was silenced, the expression levels of GSH and Glutathione peroxidase 4 (GPX4) were increased, while the expression levels of transferrin receptor 1 (TFR1), acyl-CoA synthetase long-chain family member 4 (ACSL4), Superoxide dismutase (SOD), and Malondialdehyde (MDA) were decreased. However, when an NLRP1 activator was applied, we observed the opposite phenomenon. We further explored the mechanisms underlying the actions of ferroptosis to inflammasomes. The expression levels of NLRP1, NLRP3, IL-1β, and caspase-1 were positively correlated with the ferroptosis following the application of ferroptosis inhibitor (ferrostatin-1) and ferroptosis activator (erastin). The existence of ferroptosis was demonstrated in the oxidative stress model of placental trophoblast cells; the results also indicate ferroptosis is linked with the expression of NLRP1 inflammasome. These findings may provide a valuable therapeutic target for the pathogenesis of pregnancy-related diseases.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The Ferroptosis-NLRP1 Inflammasome: The Vicious Cycle of an Adverse Pregnancy

Gao

Kang

et al. 2021

Front. Cell Dev. Biol.

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“…The HTR-8/SVneo human trophoblast cell line applied in the present study is more similar to primary trophoblasts and normal human physiological conditions. Our previous study showed that the H 2 O 2 treatment of HTR-8/SVneo cells could establish a placental oxidative stress model and simulate the mechanism of recurrent abortion in vitro (37).…”

Section: Discussionmentioning

confidence: 99%

Identification of the Active Constituents and Significant Pathways of Bushen Huoxue Decoction for the Treatment of Recurrent Spontaneous Abortion Based on Network Pharmacology

Wu²,

Kang

et al. 2020

Preprint

Self Cite

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Background: To explore Bushen Huoxue Decoction (BHD) mechanism in recurrent spontaneous abortion (RSA).Methods: We predicted and screened the action targets of four Traditional Chinese Medicine representatives by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform, and searched the disease targets of RSA through Drugbank, DisGeNET, and TTD databases. According to the obtained drug targets and disease targets, the "drug target-disease target" interaction network was further analyzed and constructed. The core target of BHD for treating RSA was were imported to establish in STRING. GO and KEGG pathway analysis were conducted with the RStudio (ggplot2). Finally, HTR-8/SVneo cells were selected to establish a cell model of oxidative stress, and the network pharmacologic results of BHD-RSA were verified by cell biology, Western blot and qRT-PCR.Results: A total of 73 active compounds were obtained from 1084 ingredients present in the BHD, and 125 genes were closely related to RSA. According to the "drug target-disease target" interaction network analysis, 26 core targets of BHD for treating RSA were finally selected, and 203 biological processes, 10 molecular functions, and 10 cell components were enriched by GO function enrichment. KEGG pathway enrichment related pathways, a total of 19, are mainly associated with a Neuroactive ligand-receptor interaction pathway. Experimental results show that compared with the oxidative stress cell model of RSA, BHD increases the expression of PTGFR, AGTR1 and OXTR mRNA by upregulating the expression of PTGFR, AGTR1 and OXTR protein, which may interfere with the occurrence and development of RSA through Neuroactive ligand-receptor interaction pathway.Conclusion: Combined with the pathological mechanism of RSA and the absence of specific signaling pathways, we hypothesized that the BHD might play a role in tonifying the kidney, strengthening the bone, promoting blood circulation, and removing blood stasis，it also can virtually relieve the symptoms of RSA, and our network pharmacological analysis lays the foundation for future clinical research.These results may help define the possible roles the BHD plays in RSA through Neuroactive ligand-receptor interaction pathway.

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“…2.1. Establishment of an Oxidative Stress Model of HTR-8/SVneo Cells [20]. HTR-8/SVneo cells (provided by Dr. Charles Graham, Queen's University of Canada) were cultured in DMEM/F12 medium (GIBCO, USA), 10% inactivated fetal bovine serum (GIBCO), and 1% penicillinstreptomycin (GIBCO) at 37°C and 5% CO 2 until the cell logarithmic growth stage.…”

Section: Methodsmentioning

confidence: 99%

Autophagy in the HTR‐8/SVneo Cell Oxidative Stress Model Is Associated with the NLRP1 Inflammasome

Sun

et al. 2021

Oxidative Medicine and Cellular Longevity

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We investigated whether there was activation of NLRP1 inflammasomes and excessive autophagy in oxidative stress damage. And we further demonstrate whether there is a cascade relationship between the activation of NLRP1 inflammasomes and the phenomenon of excessive autophagy. To observe the expression level of the NLRP1 inflammasome group in the pathological process of trophoblast cell oxidative stress, western blot, immunofluorescence, and qRT-PCR were performed. Autophagy in trophoblast cells after the action of H2O2 was detected by using normal trophoblast cells’ NLRP1-specific activator (MDP) as a positive control. The presence of excessive autophagy was determined by comparing it with the autophagy-related proteins in normal trophoblast cells. Through siRNA-NLRP1, we investigated the role of oxidative stress and the NLRP1 inflammasome in autophagy in cells. 100 μmol MDP for 24 hours can be used as the optimal concentration of the NLRP1 activator. In human placental trophoblast oxidative stress, the model group significantly increased the expression level of inflammasome IL-1β, CASP1, and NLRP1, compared with the control group NLRP3, and LC3-II, Beclin-1, ATG5, ATG7, and p62 overactivated the autophagy ability of cells. After the activation of NLRP1, the expression of these inflammasomes increased, accompanied by the decrease in autophagy. After the expression of NLRP1 was silenced by RNAi, the expression of inflammasome IL-1β, CASP1, and NLRP3 was also decreased. Still, the autophagy level was increased, which was manifested by the high expression of LC3-II, Beclin-1, ATG5, and ATG7 and the decrease in p62. Trophoblast cells showed the expression of NLRP1 protein and excessive autophagy under oxidative stress. Simultaneously, the NLRP1 inflammasome of trophoblast cells in the state of oxidative stress was correlated with autophagy. Inflammasome activation and autophagy were shown to be linked and to influence each other mutually. These may also provide new therapeutic targets in a pathological pregnancy.

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Effects of resveratrol on autophagy and the expression of inflammasomes in a placental trophoblast oxidative stress model

Cited by 18 publications

References 59 publications

The Ferroptosis-NLRP1 Inflammasome: The Vicious Cycle of an Adverse Pregnancy

The Ferroptosis-NLRP1 Inflammasome: The Vicious Cycle of an Adverse Pregnancy

Identification of the Active Constituents and Significant Pathways of Bushen Huoxue Decoction for the Treatment of Recurrent Spontaneous Abortion Based on Network Pharmacology

Autophagy in the HTR‐8/SVneo Cell Oxidative Stress Model Is Associated with the NLRP1 Inflammasome

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