Quercetin antagonizes imidacloprid-induced mitochondrial apoptosis through PTEN/PI3K/AKT in grass carp hepatocytes

Environmental Toxicology

Zhang

Zou

et al. 2022

Self Cite

Dibutyl phthalate (DBP) is a phthalic acid ester (PAE) that has posed a health hazard to the organisms. Naringenin (NRG) is a flavanone compound that has shown protection against several environmental chemicals through suppression of oxidative stress and activation of phosphatidylinositol 3-kinase/threonine kinase (PI3K/AKT) signaling pathway. Herein, swine testis (ST) cells were treated with 1.8 μM of DBP or/and 25.39 nM of NRG for 24 h, we described the discovery path of NRG inhibition on apoptosis in DBP-exposed ST cells through targeting phosphatase and tensin homologue deleted on chromosome 10 (PTEN). We first found that the anti-apoptosis effect of NRG is dependent on mitochondrial pathway through flow cytometry and related gene/protein expression, and then we detected PI3K/AKT pathway-related gene/protein expression, and established a computational docking assay between NRG and PTEN. We found that NRG specifically binds to three basic residues (His93, Lys125, Lys128) of P loop in PTEN, as well as phosphatase domains (Asp92, His93, Cys124, Lys125, Ala126, Lys128, and Arg130) in active dephosphorylation pockets, thereby reducing PTEN level and activating PI3K/AKT signaling pathway, and further inhibiting oxidative stress and mitochondrial pathway apoptosis. Taken together, our results push forward that NRG deserves further attention as a potential antagonistic therapy against DBP through targeting PTEN to inhibit oxidative stress and activate PI3K/AKT signaling pathway.

Section: Resultsmentioning

confidence: 99%

Dibutyl phthalate‐induced oxidative stress and apoptosis in swine testis cells and therapy of naringenin via PTEN/PI3K/AKT signaling pathway

Environmental Toxicology

Zhang

Zou

et al. 2022

Self Cite

“…Cytotoxicity rate increased significantly with the increase of BPA concentration ( p < 0.05), and 50% cytotoxic concentration (CC 50 ) was 220.70 ± 8.81 nM (Figure S1B). According to previous literature, 39 we usually choose 20.00%–35.00% of cytotoxicity rate for toxicant to treat cells. Therefore, 125 nM of BPA in the present study was used for further cell studies.…”

Section: Resultsmentioning

confidence: 99%

“…In addition, several studies have shown that oxidative stress causes mitochondrial damage, characterized by loss of the mitochondrial membrane potential, the release of Cytc into the cytosol, and activation of Caspase 9 and Caspase 3, ultimately activating apoptosis. 39,48 In addition, the Bcl-2 protein family is a key factor in apoptosis and regulates mitochondrial membrane potential, among which the most important members are the Bax and Bcl-2. 49 Here, we estimated apoptosis via AO/EB, Annexin V-FITC and JC-1 assays, as well as determining the levels of Cytc, Caspase 9, Caspase 3, Bax and Bcl-2, and also observed mitochondrial pathway apoptosis in BPA treated ST cells, suggesting that BPA also induced apoptosis via oxidative stress-mediated mitochondrial pathway in ST cells (Figures 3 and 4), and additionally according to the existing reports, 39,49 we detected the total mRNA and protein expression of Cytc and did not analyze the differential distribution of Cytc in mitochondria and cytosol, and we will assess them in future work.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, we observed that ROS and MDA levels in BPA treated ST cells were evidently induced, and activities of SOD, CAT and Gpx were significantly reduced (Figure 2), indicating that oxidative stress occurred during BPA exposure in ST cells. In addition, several studies have shown that oxidative stress causes mitochondrial damage, characterized by loss of the mitochondrial membrane potential, the release of Cytc into the cytosol, and activation of Caspase 9 and Caspase 3, ultimately activating apoptosis 39,48 . In addition, the Bcl‐2 protein family is a key factor in apoptosis and regulates mitochondrial membrane potential, among which the most important members are the Bax and Bcl‐2 49 .…”

Section: Discussionmentioning

confidence: 99%

“…39,48 In addition, the Bcl-2 protein family is a key factor in apoptosis and regulates mitochondrial membrane potential, among which the most important members are the Bax and Bcl-2. 49 Here, we estimated apoptosis via AO/EB, Annexin V-FITC and JC-1 assays, as well as determining the levels of Cytc, Caspase 9, Caspase 3, Bax and Bcl-2, and also observed mitochondrial pathway apoptosis in BPA treated ST cells, suggesting that BPA also induced apoptosis via oxidative stress-mediated mitochondrial pathway in ST cells (Figures 3 and 4), and additionally according to the existing reports, 39,49 we detected the total mRNA and protein expression of Cytc and did not analyze the differential distribution of Cytc in mitochondria and cytosol, and we will assess them in future work. In order to explore the mechanism of oxidative stressinduced mitochondrial pathway apoptosis caused by BPA, we investigated the Keap1/Nrf2 signaling pathway as it is an important antioxidant defense strategy, and especially it has been shown that BPA down-regulated Nrf2 levels in livers of male mice 19 and in hippocampal tissue of female mice, 23 and thus resulted in hepatic and hippocampal oxidative stress.…”

Section: Discussionmentioning

confidence: 99%

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Naringenin protects swine testis cells from bisphenol A‐induced apoptosis via Keap1/Nrf2 signaling pathway

Lü

2021

BioFactors

Self Cite

Bisphenol A (BPA) has caused serious pathologies in varying organs of humans and animals, especially reproductive organs. Naringenin (NRG) is a flavanone compound that has shown protective effects against several environmental chemicals through suppression of oxidative stress and activation of nuclear factor erythroid 2-related factor 2 (Nrf2) pathway. Herein, we described the discovery path of NRG inhibition on apoptosis in BPA exposed swine testis (ST) cells through targeting Kelch-like ech-associated protein (Keap1). We found that NRG could specifically bound to the active residues of DGR domain in Keap1, thereby activating Nrf2 signaling pathway, and then increasing the levels of SOD, GPx and CAT, and finally inhibiting oxidative stress and mitochondrial apoptosis induced by BPA in ST cells. Altogether, our results showed that NRG inhibits oxidative stress and mitochondrial apoptosis induced by BPA in ST cells by targeting Keap1/Nrf2 signaling pathway, indicating that NRG could serve as an antagonistic therapy against BPA.

Bisphenol A aggravates renal apoptosis and necroptosis in selenium‐deficient chickens via oxidative stress and PI3K/AKT pathway

Journal Cellular Physiology

Zhang

Zou

et al. 2022

Self Cite

Bisphenol A (BPA) in the environment can have deleterious effects on humans and animals. BPA can exert nephrotoxicity by inducing oxidative stress. Selenium (Se) deficiency can specifically impair kidney tissues and additionally show a synergistic effect on the toxicity of several environmental chemicals. However, the toxic effects of BPA on the chicken kidney and whether Se deficiency produces synergistic effects on the toxicity of BPA remain poorly understood. Herein, we established BPA exposure models and Se deficiency model in vivo and in vitro, and described the discovery path of BPA aggravation on apoptosis and necroptosis in Se-deficient chicken kidneys via regulation of oxidative stress and phosphatidylinositol 3-kinase/ threonine kinase (PI3K/AKT) signaling pathway. We found that BPA exposure increased reactive oxygen species and malondialdehyde levels, reduced activities of catalase, GPx, and superoxide dismutase, downregulated PI3K and AKT expressions, activated Bcl/Bax-Caspase 9-Caspase 3, and receptor-interacting protein kinase 1/mixed lineage kinase domain-like protein signaling pathways, resulting in apoptosis and necroptosis in the chicken kidney. In addition, Se deficiency significantly promoted the expression of renal apoptosis and necroptosis in BPA-exposed chicken kidneys. Altogether, our results showed that BPA aggravates apoptosis and necroptosis in Sedeficient chicken kidneys via regulation of oxidative stress and PI3K/AKT signaling pathway. Our findings elucidate the mechanism of BPA nephrotoxicity and Se deficiency exacerbation toxicity in chickens and will provide great significance for the protection of the ecological environment and animal health.