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Glycine ameliorates MBP-induced meiotic abnormalities and apoptosis by regulating mitochondrial-endoplasmic reticulum interactions in porcine oocytes
2022
Gao, Lepeng | Zhang, Chang | Yu, Sicong | Liu, Shuang | Wang, Guoxia | Lan, Hainan | Zheng, Xin | Li, Suo
Monobutyl phthalate (MBP) is the main metabolite of dibutyl phthalate (DBP) in vivo. MBP has a stable structure, can continuously accumulate in living organisms, and has the potentially to harm animal and human reproductive function. In the ovarian follicle microenvironment, MBP may lead to defects in follicular development and steroid production, abnormal meiotic maturation, impaired ovarian function and other reproductive deficits. In this study, SMART-seq was used to investigate the effects of MBP exposure on the in vitro maturation (IVM) and development of porcine oocytes. The results showed that differentially expressed genes after MBP exposure were enriched in the biological processes cytoskeleton, cell apoptosis, endoplasmic reticulum (ER) and mitochondria. Glycine (Gly) improved the developmental potential of porcine oocytes by regulating mitochondrial and ER function. The effect of Gly in protecting oocytes against MBP-induced damage was studied. The results showed that the addition of Gly significantly decreased the rate of MBP-induced spindle abnormalities, decreased the frequency of MBP-induced mitochondria-associated ER membrane (MAM) interactions, and downregulated the protein and gene expression of the linkage molecules Mitofusin 1 (MFN1) and Mitofusin 2 (MFN2) in the MAM. Additionally, treatment with Gly restored the distribution of the 1,4,5-triphosphate receptor 1 (IP₃R1) and voltage-dependent anion channel 1 (VDAC1), further decreasing the intracellular free calcium concentration ([Ca²⁺]ᵢ) levels and mitochondrial Ca²⁺ ([Ca²⁺]ₘ) , increasing the ER Ca²⁺ ([Ca²⁺]ER) levels, and thus significantly increasing the ER levels and mitochondrial membrane potential (ΔΨ m). Gly also decreased the levels of reactive oxygen species (ROS) and increased the levels of Glutathione (GSH), oocyte apoptosis-related indicators (Caspase-3 activity and Annexin V) and oocyte apoptosis-related genes (BAX, Caspase 3 and AIFM1). Our results suggest that Gly can ameliorate microtubule cytoskeleton abnormalities and improve oocyte maturation by reducing the defective mitochondrial–ER interactions caused by MBP exposure in vitro.
显示更多 [+] 显示较少 [-]Bioimaging revealed contrasting organelle-specific transport of copper and zinc and implication for toxicity
2022
Yuan, Liuliang | Wang, Wen-Xiong
Zn and Cu are two of the essential trace elements and it is important to understand the regulation of their distribution on cellular functions. Herein, we for the first time investigated the subcellular fate and behavior of Zn and Cu in zebrafish cells through bioimaging, and demonstrated the completely different behaviors of Zn and Cu. The distribution of Zn²⁺ was concentration-dependent, and Zn²⁺ at low concentration was predominantly located in the lysosomes (76.5%). A further increase of cellular Zn²⁺ resulted in a spillover and more diffusive distribution, with partitioning to mitochondria and other regions. In contrast, the subcellular distribution of Cu⁺ was time-dependent. Upon entering the cells, Cu²⁺ was reduced to Cu⁺, which was first concentrated in the mitochondria (71.4%) followed by transportation to lysosomes (58.6%), and finally removal from the cell. With such differential transportation, Cu²⁺ instead of Zn²⁺ had a negative effect on the mitochondrial membrane potential and glutathione. Correspondingly, the pH of lysosomes was more sensitive to Zn²⁺ exposure and decreased with increasing internalized Zn²⁺, whereas it increased upon Cu²⁺ exposure. The responses of cellular pH showed an opposite pattern from the lysosomal pH. Lysosome was the most critical organelle in response to incoming Zn²⁺ by increasing its number and size, whereas Cu²⁺ reduced the lysosome size. Our study showed that Zn²⁺ and Cu²⁺ had completely different cellular handlings and fates with important implications for understanding of their toxicity.
显示更多 [+] 显示较少 [-]Mechanism of thorium-nitrate and thorium-dioxide induced cytotoxicity in normal human lung epithelial cells (WI26): Role of oxidative stress, HSPs and DNA damage
2021
Das, Sourav Kumar | Ali, Manjoor | Shetake, Neena G. | Dumpala, Rama Mohan R. | Pandey, Badri N. | Kumar, Amit
Inhalation represents the most prevalent route of exposure with Thorium-232 compounds (Th-nitrate/Th-dioxide)/Th-containing dust in real occupational scenario. The present study investigated the mechanism of Th response in normal human alveolar epithelial cells (WI26), exposed to Th-nitrate or colloidal Th-dioxide (1–100 μg/ml, 24–72 h). Assessment in terms of changes in cell morphology, cell proliferation (cell count), plasma membrane integrity (lactate dehydrogenase leakage) and mitochondrial metabolic activity (MTT reduction) showed that Th-dioxide was quantitatively more deleterious than Th-nitrate to WI26 cells. TEM and immunofluorescence analysis suggested that Th-dioxide followed a clathrin/caveolin-mediated endocytosis, however, membrane perforation/non-endocytosis seemed to be the mode of Th internalization in cells exposed to Th-nitrate. Th-estimation by ICP-MS showed significantly higher uptake of Th in cells treated with Th-dioxide than with Th-nitrate at a given concentration. Both Th-dioxide and nitrate were found to increase the level of reactive oxygen species, which seemed to be responsible for lipid peroxidation, alteration in mitochondrial membrane potential and DNA-damage. Amongst HSPs, the protein levels of HSP70 and HSP90 were affected differentially by Th-nitrate/dioxide. Specific inhibitors of ATM (KU55933) or HSP90 (17AAG) were found to increase the Th- cytotoxicity suggesting prosurvival role of these signaling molecules in rescuing the cells from Th-toxicity.
显示更多 [+] 显示较少 [-]Impact of wildfires on SO2 detoxification mechanisms in leaves of oak and beech trees
2021
Weber, Jan-Niklas | Kaufholdt, David | Minner-Meinen, Rieke | Bloem, Elke | Shahid, Afsheen | Rennenberg, H. (Heinz) | Hänsch, Robert
Frequency and intensity of wildfire occurrences are dramatically increasing worldwide due to global climate change, having a devastating effect on the entire ecosystem including plants. Moreover, distribution of fire-smoke can influence the natural environment over very long distances, i.e. hundreds of kilometres. Dry plant matter contains 0.1–0.9% (w/w) sulphur, which is mainly released during combustion into the atmosphere as sulphur dioxide (SO₂) resulting in local concentrations of up to 3000 nL L⁻¹. SO₂ is a highly hazardous gas, which enters plants mostly via the stomata. Toxic sulphite is formed inside the leaves due to conversion of SO₂. Plants as sessile organisms cannot escape from threats, why they evolved an impressive diversity of molecular defence mechanisms. In the present study, two recent wildfires in Germany were evaluated to analyse the effect of SO₂ released into the atmosphere on deciduous trees: the Meppen peat fire in 2018 and the forest fire close to Luebtheen in 2019. Collected leaf material from beech (Fagus sylvatica) and oak (Quercus robur) was examined with respect to detoxification of sulphur surplus due to the exposure to elevated SO₂. An induced stress reaction in both species was indicated by a 1.5-fold increase in oxidized glutathione. In beech leaves, the enzymatic activities of the sulphite detoxification enzymes sulphite oxidase and apoplastic peroxidases were increased 5-fold and a trend of sulphate accumulation was observed. In contrast, oaks did not regulate these enzymes during smoke exposure, however, the constitutive activity is 10-fold and 3-fold higher than in beech. These results show for the first time sulphite detoxification strategies of trees in situ after natural smoke exposure. Beech and oak trees survived short-term SO₂ fumigation due to exclusion of toxic gases and different oxidative detoxification strategies. Beeches use efficient upregulation of oxidative sulphite detoxification enzymes, while oaks hold a constitutively high enzyme-pool available.
显示更多 [+] 显示较少 [-]Hyperaccumulation of Cd by Rorippa globosa (Turcz.) Thell. from soil enriched with different Cd compounds, and impact of soil amendment with glutathione (GSH) on the hyperaccumulation efficiency
2019
Dou, Xuekai | Dai, Huiping | Twardowska, Irena | Wei, Shuhe
Rorippa globosa (Turcz.) Thell. is known as Cd hyperaccumulator, however neither hyperaccumulation nature, nor affecting factors like the effect of Cd compounds entering soil from different sources, or of specific soil amendments, are not yet satisfactorily clarified. In the pot culture experiment, Cd accumulation by R. globosa from soils spiked with 3 and 9 mg Cd kg⁻¹ in the form of Cd(NO₃)₂, CdCl₂, CdBr₂, CdI₂, CdSO₄, CdF₂, Cd(OH)₂, CdCO₃, Cd₃(PO₄)₂, CdS and effect of soil amendment with glutathione (GSH) were investigated. Accumulation capacity of R. globosa for Cd appeared to reflect its extractability in soils and was about two-fold bigger for high soluble compounds than for low-soluble ones. At that, the differences between the accumulation of Cd originating from high soluble compound group did not exceed 20%, while the differences within the low soluble compound group were insignificant (p < 0.05). The analysis of Cd uptake, uptake factor (UF), enrichment factor (EF) and translocation factor (TF) patterns revealed that Cd hyperaccumulating properties of R. globosa are based on the high water/nutrients demand and strong tolerance to Cd, although weak protection against Cd uptake by root system was also observed. Amendment with GSH enhanced Cd availability to plant and its uptake from soil, but exerted no effect on Cd translocation in plants. In the light of the results, the use of R. globosa for phytoremediation of moderately polluted agricultural lands as forecrop or aftercrop, and the GSH-assisted phytoremediation of highly polluted post-industrial sites seem to be viable options.
显示更多 [+] 显示较少 [-]Oxidative potential of particulate matter 2.5 as predictive indicator of cellular stress
2017
Crobeddu, Bélinda | Aragao-Santiago, Leticia | Bui, Linh-Chi | Boland, Sonja | Baeza Squiban, Armelle
Particulate air pollution being recognized to be responsible for short and long term health effects, regulations for particulate matter with an aerodynamic diameter less than 2.5 (PM2.5) are more and more restrictive. PM2.5 regulation is based on mass without taking into account PM2.5 composition that drives toxicity. Measurement of the oxidative potential (OP) of PM could be an additional PM indicator that would encompass the PM components involved in oxidative stress, the main mechanism of PM toxicity. We compared different methods to evaluate the intrinsic oxidative potential of PM2.5 sampled in Paris and their ability to reflect the oxidative and inflammatory response in bronchial epithelial cells used as relevant target organ cells. The dithiothreitol depletion assay, the antioxidant (ascorbic acid and glutathione) depletion assay (OPAO), the plasmid scission assay and the dichlorofluorescein (DCFH) oxidation assay used to characterize the OP of PM2.5 (10–100 μg/mL) provided positive results of different magnitude with all the PM2.5 samples used with significant correlation with different metals such as Cu and Zn as well as total polyaromatic hydrocarbons and the soluble organic fraction. The OPAO assay showed the best correlation with the production of intracellular reactive oxygen species by NCI-H292 cell line assessed by DCFH oxidation and with the expression of anti-oxidant genes (superoxide dismutase 2, heme-oxygenase-1) as well as the proinflammatory response (Interleukin 6) when exposed from 1 to 10 μg/cm2. The OPAO assay appears as the most prone to predict the biological effect driven by PM2.5 and related to oxidative stress.
显示更多 [+] 显示较少 [-]The association between bisphenol A exposure and oxidative damage in rats/mice: A systematic review and meta-analysis
2022
Zhang, Huan | Yang, Rui-fu | Shi, Wanying | Zhou, Xin | Sun, Suju
Numerous studies reported that BPA could cause oxidative damage to different tissues in rats/mice. This study aimed to perform a systematic review and meta-analysis of BPA exposure on oxidative damage in rats/mice. A comprehensive literature search was conducted using PubMed, Embase, and Web of Science databases from their inception date until July 18, 2020. 20 eligible articles were included in this study. The results showed that BPA could significantly increase the level of MDA (SMD, 16.88; 95%CI, 12.06–21.71), but there was a significant reduction in the contents of antioxidants, such as GR (−10.46, −13.91 ∼ −7.02), CAT (−8.48, −11.66 ∼ −5.30), GPx (−9.37, −11.95 ∼ −6.80), GST (−7.59, −14.51 ∼ −0.67), GSH (−10.64, −13.96 ~ −7.33), and SOD (−6.48, −8.37 ∼ −4.58) in rats/mice. Our study provided clear evidence that BPA exposure could significantly induce oxidative damage in rats/mice. And we also found that the degree of oxidative damage was related to BPA dose, target tissue, intervention means, and exposure duration of BPA.
显示更多 [+] 显示较少 [-]Plasma perfluoroalkyl substance exposure and incidence risk of breast cancer: A case-cohort study in the Dongfeng-Tongji cohort
2022
Feng, Yue | Bai, Yansen | Lu, Yanjun | Chen, Mengshi | Fu, Ming | Guan, Xin | Cao, Qiang | Yuan, Fangfang | Jie, Jiali | Li, Mengying | Meng, Hua | Wang, Chenming | Hong, Shiru | Zhou, Yuhan | Zhang, Xiaomin | He, Meian | Kwok, Woon
Experimental studies have suggested perfluoroalkyl substances (PFASs) as mammary toxicants, but few studies evaluated the prospective associations of PFASs with breast cancer risk. We performed a case-cohort study within the Dongfeng-Tongji cohort, including incident breast cancer cases (n = 226) and a random sub-cohort (n = 990). Baseline plasma concentrations of four perfluorinated carboxylic acids (PFCAs) [perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), and perfluoroheptanoic acid (PFHpA)] and two perfluorinated sulfonic acids (PFSAs) [perfluorooctane sulfonic acid (PFOS) and perfluorohexane sulfonic acid (PFHxS)] were measured. Barlow-weighted Cox regression models revealed that each 1-unit increase in ln-transformed PFOA and PFHpA was associated with a separate 35% and 20% elevated incident risk of breast cancer [HR(95%CI) = 1.35(1.03, 1.78) and 1.20(1.02, 1.40), respectively], which were also significant among postmenopausal females [HR(95%CI) = 1.34(1.01, 1.77) and 1.23 (1.02, 1.48), respectively]. Quantile g-computation analysis observed a 19% increased incident risk of breast cancer along with each simultaneous quartile increase in all ln-transformed PFCA concentrations [HR(95%CI) = 1.19(1.01, 1.41)], with PFOA accounting for 56% of the positive effect. Our findings firstly revealed the impact of short-chain PFHpA on increased incident risk of breast cancer, suggested exposure to PFASs as a risk factor for breast cancer, and shed light on breast cancer prevention by regulating PFASs as a chemical class.
显示更多 [+] 显示较少 [-]Hsp27, a potential EcR target, protects nonylphenol-induced cellular and organismal toxicity in Drosophila melanogaster
2022
Dwivedi, Shiwangi | D'Souza, Leonard Clinton | Shetty, Nidhi Ganesh | Raghu, Shamprasad Varija | Sharma, Anurag
Deciphering the potential mechanism of chemical-induced toxicity enables us to alleviate the cellular and organismal dysfunction. The environmental presence of nonylphenol (endocrine disruptor) has a major health concern due to its widespread usage in our day-to-day life. The current study establishes a novel functional link among nonylphenol-induced oxidative stress, Heat shock protein 27 (Hsp27, member of stress protein family), and Ecdysone receptor (EcR, a nuclear receptor), which eventually coordinates the nonylphenol-induced sub-cellular and organismal level toxicity in a genetically tractable model Drosophila melanogaster. Drosophila larvae exposed to nonylphenol (0.05, 0.5 and 5.0 μg/mL) showed a significant decrease in Hsp27 and EcR mRNA levels in the midgut. In concurrence, reactive oxygen species (ROS) levels were increased with a corresponding decline in glutathione (GSH) level and Thioredoxin reductase (TrxR) activity. Increased lipid peroxidation (LPO), protein carbonyl (PC) contents, and cell death were also observed in a correlation with the nonylphenol concentrations. Sub-cellular toxicity poses a negative organismal response, which was evident by delayed larval development and reduced Drosophila emergence. Subsequently, a positive genetic correlation (p < 0.001) between EcR and Hsp27 revealed that nonylphenol-dependent EcR reduction is a possible link for the downregulation of Hsp27. Further, Hsp27 overexpression in midgut cells showed a reduction in nonylphenol-induced intracellular ROS, LPO, PC content, and cell death through the TrxR mediated regenerative pathway and reduced GSH level improving the organismal response to the nonylphenol exposure. Altogether, the study elucidates the potential EcR-Hsp27 molecular interactions in mitigating the nonylphenol-induced cellular and organismal toxicity.
显示更多 [+] 显示较少 [-]Lead accumulation in photosynthetic Euglena gracilis depends on polyphosphates and calcium
2021
Hernández-Garnica, M. | García-García, J.D. | Moreno-Sánchez, R. | Sánchez-Thomas, R.
Worldwide increasing levels of lead in water systems require the search for efficient ecologically friendly strategies to remove it. Hence, lead accumulation by the free-living algae-like Euglena gracilis and its effects on cellular growth, respiration, photosynthesis, chlorophyll, calcium, and levels of thiol- and phosphate-molecules were analyzed. Photosynthetic cells were able to accumulate 4627 mg lead/kgDW after 5 days of culture with 200 μM Pb²⁺. Nevertheless, exposure to 50, 100 and 200 μM Pb²⁺ for up to 8 days did not modify growth, viability, chlorophyll content and oxygen consumption/production. Enhanced biosynthesis of thiol molecules and polyphosphates, i.e. the two canonical metal ion chelation mechanisms in E. gracilis, was not induced under such conditions. However, in cells cultured in the absence of phosphate, lead accumulation and polyphosphate content markedly decreased, while culturing in the absence of sulfate did not modify the accumulation of this metal. In turn, the total amount of intracellular calcium slightly increased as the amount of intracellular lead increased, whereas under Ca²⁺ deficiency lead accumulation doubled. Therefore, the results indicated that E. gracilis is highly resistant to lead through mechanisms mediated by polyphosphates and Ca²⁺ and can in fact be classified as a lead hyperaccumulator microorganism.
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