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Bisphenol A aggravate selenium deficiency-induced apoptosis via miR-215-3p/Dio1 to activate ROS/PI3K/AKT pathway in
1College of Veterinary Medicine, Northeast Agricultural University, Harbin, People's Republic of China.
Abstract:
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.
Insights
Bisphenol A (BPA) and selenium (Se) deficiency induce apoptosis in chicken arterial endothelial cells via the miR-215-3p/Dio1 axis, impacting cardiovascular health. This pathway involves oxidative stress and the PI3K/AKT signaling cascade.
Area of Science:
- Endocrinology and Toxicology
- Molecular Biology
- Cardiovascular Research
Background:
- Bisphenol A (BPA) and selenium (Se) deficiency are implicated in cardiovascular diseases.
- MicroRNAs (miRNAs) regulate gene expression and play a role in apoptosis, a key process in cardiovascular injury.
- Understanding the interplay between BPA, Se deficiency, and miRNAs in arterial endothelial cells is crucial for elucidating disease mechanisms.
Purpose of the Study:
- To investigate the mechanism of apoptosis induced by BPA exposure and Se deficiency in chicken arterial endothelial cells.
- To explore the role of specific microRNAs, particularly miR-215-3p, in this apoptotic process.
- To elucidate the involvement of the miR-215-3p/iodothyronine deiodinase 1 (Dio1) axis in BPA and Se deficiency-induced endothelial cell apoptosis.
Main Methods:
- Establishment of in vivo (chicken) and in vitro (PAEC cells) models of BPA exposure and Se deficiency.
- Verification of the targeting relationship between miR-215-3p and Dio1 using a double luciferase gene reporter assay.
- Assessment of oxidative stress, PI3K/AKT pathway activation, mitochondrial dynamics, apoptosis-related gene expression, and apoptosis levels using various molecular and cellular assays (qRT-PCR, Western blot, flow cytometry, TUNEL).
Main Results:
- BPA exposure and Se deficiency led to overexpression of miR-215-3p, increased oxidative stress, inhibited PI3K/AKT pathway activation, promoted mitochondrial fission, and induced apoptosis in chicken arterial endothelial cells.
- Overexpression of miR-215-3p and knockout of Dio1 were found to induce apoptosis.
- Inhibition of miR-215-3p and N-acetyl-l-cysteine (NAC) partially protected against apoptosis, while LY294002 aggravated it, highlighting the role of ROS/PI3K/AKT pathway.
Conclusions:
- BPA exposure exacerbates apoptosis in Se-deficient chicken arterial endothelial cells through the miR-215-3p/Dio1 axis, modulating the ROS/PI3K/AKT pathway.
- The miR-215-3p/Dio1 axis offers a novel perspective on the toxic mechanisms of BPA and Se deficiency.
- This study reveals a new regulatory model for apoptosis-induced vascular damage, with potential implications for cardiovascular disease research.
