Bisphenol A Induces Accelerated Cell Aging in Murine Endothelium

Moreno-Gómez-Toledano, Rafael; Sánchez-Esteban, Sandra; Cook, Alberto; Mínguez-Moratinos, Marta; Ramírez-Carracedo, Rafael; Reventún, Paula; Delgado-Marín, María; Bosch, Ricardo J.; Saura, Marta

doi:10.3390/biom11101429

Cited by 18 publications

(10 citation statements)

References 79 publications

(107 reference statements)

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“…N-acetylcysteine and genistein have been reported to play a protective role in cellular senescence ( 53 , 54 ). Bisphenol A, bleomycin, cisplatin and dexamethasone have been reported to induce cell senescence under some special circumstances ( 55 – 58 ). Moreover, conventional drugs that improve cardiac function after AMI such as the calcium sensitizer levosimendan and the angiotensin II-receptor blocker losartan have been found to reduce the expression of markers of senescence in heart tissue ( 52 ).…”

Section: Discussionmentioning

confidence: 99%

Identification and validation of senescence-related genes in circulating endothelial cells of patients with acute myocardial infarction

Xiang

Shen

Zhang

et al. 2022

Front. Cardiovasc. Med.

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BackgroundAcute myocardial infarction (AMI) is the main clinical cause of death and cardiovascular disease and thus has high rates of morbidity and mortality. The increase in cardiovascular disease with aging is partly the result of vascular endothelial cell senescence and associated vascular dysfunction. This study was performed to identify potential key cellular senescence-related genes (SRGs) as biomarkers for the diagnosis of AMI using bioinformatics.MethodsUsing the CellAge database, we identified cellular SRGs. GSE66360 and GSE48060 for AMI patients and healthy controls and GSE19322 for mice were downloaded from the Gene Expression Omnibus (GEO) database. The GSE66360 dataset was divided into a training set and a validation set. The GSE48060 dataset was used as another validation set. The GSE19322 dataset was used to explore the evolution of the screened diagnostic markers in the dynamic process of AMI. Differentially expressed genes (DEGs) of AMI were identified from the GSE66360 training set. Differentially expressed senescence-related genes (DESRGs) selected from SRGs and DEGs were analyzed using Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, and protein-protein interaction (PPI) networks. Hub genes in DESRGs were selected based on degree, and diagnostic genes were further screened by gene expression and receiver operating characteristic (ROC) curve. Finally, a miRNA-gene network of diagnostic genes was constructed and targeted drug prediction was performed.ResultsA total of 520 DEGs were screened from the GSE66360 training set, and 279 SRGs were identified from the CellAge database. The overlapping DEGs and SRGs constituted 14 DESRGs, including 4 senescence suppressor genes and 10 senescence inducible genes. The top 10 hub genes, including FOS, MMP9, CEBPB, CDKN1A, CXCL1, ETS2, BCL6, SGK1, ZFP36, and IGFBP3, were screened. Furthermore, three diagnostic genes were identified: MMP9, ETS2, and BCL6. The ROC analysis showed that the respective area under the curves (AUCs) of MMP9, ETS2, and BCL6 were 0.786, 0.848, and 0.852 in the GSE66360 validation set and 0.708, 0.791, and 0.727 in the GSE48060 dataset. In the GSE19322 dataset, MMP9 (AUC, 0.888) and ETS2 (AUC, 0.929) had very high diagnostic values in the early stage of AMI. Finally, based on these three diagnostic genes, we found that drugs such as acetylcysteine and genistein may be targeted for the treatment of age-related AMI.ConclusionThe results of this study suggest that cellular SRGs might play an important role in AMI. MMP9, ETS2, and BCL6 have potential as specific biomarkers for the early diagnosis of AMI.

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Section: Discussionmentioning

confidence: 99%

Identification and validation of senescence-related genes in circulating endothelial cells of patients with acute myocardial infarction

Xiang

Shen

Zhang

et al. 2022

Front. Cardiovasc. Med.

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“…Studies have shown that BPA exposure can cause arterial endothelial dysfunction, uterine growth restriction, and impaired fetal placental development in rats (Barberio et al, 2021). It also induces the activation of unfolded protein response and cellular senescence through oxidative stress, induces programmed necrosis of mouse aortic endothelial cells and promotes the occurrence of cardiovascular disease (Moreno‐Gómez‐Toledano et al, 2021). Exposure to BPA in healthy or malnourished mice leads to left ventricular diastolic dysfunction, fibrosis, and coronary remodeling (García‐Arévalo et al, 2021).…”

Section: Introductionmentioning

confidence: 99%

Bisphenol A aggravate selenium deficiency‐induced apoptosis via miR‐215‐3p/Dio1 to activate ROS/PI3K/AKT pathway in chicken arterial

Fan

et al. 2023

Journal Cellular Physiology

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Both bisphenol A (BPA) and selenium (Se) deficiency can affect the expression of microRNAs (miRNAs), which can specifically regulate its target mRNA and induce apoptosis, and play a significant role in cardiovascular injury diseases. To explore the mechanism of apoptosis induced by BPA and Se deficiency in chicken arterial endothelial tissue and the role of miRNAs in this process, the model of BPA exposure/Se deficiency in chicken and PAEC cells have been employed. The targeting relationship between miR‐215‐3p and iodothyronine deiodinase 1 (Dio1) in PAEC was verified by double luciferase gene report. The level of miR‐215‐3p was detected by qRT‐PCR. The oxidative stress level of arterial endothelial cells was detected by oxidative stress kit and DCFH‐DA probe method. The PI3K/AKT pathway, mitochondrial dynamics, and apoptosis‐related genes were detected by qRT‐PCR and western blot. The mitochondrial ATP level and nitric oxide synthases (NOSs) level were detected with the kit. TUNEL, acridine orange/ethidium bromide, and flow cytometry were used to detect the level of apoptosis. The results showed that BPA exposure and Se deficiency led to overexpression of miR‐215‐3p, aggravated oxidative stress, inhibited activation of PI3K/AKT pathway, promoted mitochondrial division, increased expression of apoptosis related genes, and finally led to apoptosis of chicken arterial endothelial cells. We also established knockdown/overexpression models of miR‐215‐3p and Dio1 in vitro, and found that overexpression of miR‐215‐3p and knockout of Dio1 can induce apoptosis. Interestingly, miR‐215‐3p‐Inhibitor and N‐acetyl‐ l‐cysteine (NAC) partially prevented apoptosis caused by BPA exposure and Se deficiency, and LY294002 aggravated apoptosis. These results suggest that BPA exposure aggravates the apoptosis of Se deficient arterial endothelial cells in chickens by regulating the ROS/PI3K/AKT pathway activated by miR‐215‐3p/Dio1. The miR‐215‐3p/Dio1 axis provides a new way to understand the toxic mechanism of BPA exposure and Se deficiency, and reveals a new regulatory model of apoptosis damage in vascular diseases.

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“…Both its production and recycling involve the release of pollutants, xenobiotic compounds that should not be found in the air, rivers, or the human population[ 1 , 2 ]. One of the most important, due to its wide distribution and variety of biological effects, is bisphenol A (BPA)[ 3 - 6 ]. The European Chemicals Agency has recently included BPA within the Candidate List of substances of very high concern due to its properties as an endocrine disruptor and its potentially harmful effect on reproduction[ 7 ].…”

Section: Introductionmentioning

confidence: 99%

Association between urinary concentrations of bisphenol A substitutes and diabetes in adults

Moreno-Gómez-Toledano¹,

Vélez²,

Arenas³

et al. 2022

WJD

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BACKGROUND Due to new restrictions on the use of bisphenol A (BPA), industries are beginning to replace it with derived molecules such as bisphenol S and F (BPS and BPF). There is extensive evidence in the academic literature on the potential health effects of BPA, which is known to be a diabetogenic molecule. However, there are few publications related to new compounds derived from BPA. AIM To perform an epidemiological study of urinary BPS and BPF in the American National Health and Nutrition Examination Survey (NHANES) cohort, and analyze their possible relationship with diabetes mellitus. METHODS NHANES datasets from 2013 to 2016 were used due to the urinary BPF and BPS availability. Data from 3658 adults were analyzed to perform regression analysis exploring the possible relationship between BPA-derived compounds and diabetes. RESULTS Descriptive statistics, linear regression modeling, and logistic regression analysis revealed a significant relationship between urinary BPS, but not BPF, and diabetes risk. Additionally, a relationship was observed between both compounds and hypertension and a slight relationship between BPF and dyslipidemia. CONCLUSION In the present study, a strong relationship between urinary BPS, not BPF, and diabetes risk has been determined. BPA substitute molecules do not exempt the population from potential health risks.

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Bisphenol A Induces Accelerated Cell Aging in Murine Endothelium

Cited by 18 publications

References 79 publications

Identification and validation of senescence-related genes in circulating endothelial cells of patients with acute myocardial infarction

Identification and validation of senescence-related genes in circulating endothelial cells of patients with acute myocardial infarction

Bisphenol A aggravate selenium deficiency‐induced apoptosis via miR‐215‐3p/Dio1 to activate ROS/PI3K/AKT pathway in chicken arterial

Association between urinary concentrations of bisphenol A substitutes and diabetes in adults

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