The mitochondrial and endoplasmic reticulum pathways involved in the apoptosis of bursa of Fabricius cells in broilers exposed to dietary aflatoxin B1

Yuan, Shibin; Wu, Biao; Yu, Zhengqiang; Fang, Jing; Liang, Na; Zhou, Ming-Qiang; Huang, Cheng; Peng, Xi

doi:10.18632/oncotarget.11321

Cited by 42 publications

(34 citation statements)

References 46 publications

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“…As for BF, this apoptotic pathway even hasn't been activated by As 2 O 3 in present study. Our result is in line with previous study which showed the expressions of Fas, FasL, FADD and caspase-8 were no difference between the Aflatoxin B 1 group and the control group, which evidenced that death receptor apoptotic pathway may not contribute to the excessive cell death of BF cells [41]. In summary, mitochondria apoptosis pathway plays a more extensive role than death receptor apoptotic pathway in chicken immune organs suffering from subchronic arsenism, and the latter pathway might be inhibited in BF cells, its exact mechanism needs further study.…”

Section: Discussionsupporting

confidence: 92%

Subchronic arsenism-induced oxidative stress and inflammation contribute to apoptosis through mitochondrial and death receptor dependent pathways in chicken immune organs

Zhao

et al. 2017

Oncotarget

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In many organ dysfunctions, arsenic and its compounds are well known to induce apoptosis by the mitochondria and death receptor apoptotic pathways in liver and airway. However, it is less reported that which signaling pathways contribute to excessive apoptosis of chicken immune organs, a major target of toxic metals biotransformation, which suffer from subchronic arsenism. In this study, we investigated whether the mitochondria or death receptor apoptotic pathways activated in the immune organs (spleen, thymus and bursa of Fabricius) of one-day-old male Hy-line chickens exposed to arsenic trioxide (As2O3), which were fed on diets supplemented with 0, 0.625, 1.25 and 2.5 mg/kg BW of As2O3 for 30, 60 and 90 days. We found that (1) Oxidative damage and inflammatory response were confirmed in the immune organs of chickens fed on As2O3 diet. (2) Subchronic arsenism induced typical apoptotic changes in ultrastructure. (3) TdT-mediated dUTP Nick-End Labeling (TUNEL) showed that the number of apoptotic cells significantly increased under subchronic arsenism. (4) As2O3-induced apoptosis of immune organs involved in mitochondrial pathway (decrease of B-cell lymphoma-2 (Bcl-2) and increase of protein 53 (p53), Bcl-2 Associated X Protein (Bax), caspase-9, caspase-3) and death receptor pathway (increase of factor associated suicide (Fas) and caspase-8). In conclusion, this work is the first to demonstrate that the activation of mitochondria and death receptor apoptosis pathways can lead to excessive apoptosis in immune organs of chickens, which suffer from subchronic arsenism, meanwhile, oxidative stress as well as subsequent inflammatory is a crucial driver of apoptosis.

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Section: Discussionsupporting

confidence: 92%

Subchronic arsenism-induced oxidative stress and inflammation contribute to apoptosis through mitochondrial and death receptor dependent pathways in chicken immune organs

Zhao

et al. 2017

Oncotarget

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“…Bcl-2-shRNA inhibited the expression of the Bcl-2 gene and thereby changed the proportion of Bcl-2/Bax, thus enhancing the expression of the pro-apoptotic gene Bax. Bax is a promoter of the mitochondrial pathway that promotes the release of CytC, activates Caspase-3 and induces apoptosis of synoviocytes (27).…”

Section: Discussionmentioning

confidence: 99%

Construction of a Bcl-2-shRNA expression vector and its effect on the mitochondrial apoptosis pathway in SW982 cells

Zhang

Xue

2017

Int J Mol Med

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Apoptosis is considered to serve an important role in the pathogenesis of rheumatoid arthritis. The aim of the present study was to construct Bcl-2-short hairpin (sh)RNA expression vectors and transfect them into human synovial sarcoma SW982 cells, in order to screen for an effective interference sequence and analyze the effects of this interference on the expression levels of Bcl-2 and other molecules associated with the mitochondrial apoptosis pathway. Three different shRNAs (Bcl-2-sh1, 2 and 3) were designed according to the human Bcl-2 mRNA target sequence and were transformed into competent DH5α Escherichia coli cells following the construction of an expression vector, which was then transfected into SW982 cells. SW982 cells were grouped into a control group (transfected with a negative control shRNA), and Bcl-2-sh1, Bcl-2-sh2 and Bcl-2-sh3 groups (transfected with Bcl-2-sh1, 2 and 3, respectively). The expression levels of Bcl-2 mRNA were detected using reverse transcription-quantitative PCR (RT-qPCR). Bcl-2-sh1 was identified as the most effective shRNA sequence for interference, and was used for subsequent experiments. The mRNA and protein expression levels of Bcl-2, Bax, CytC and Caspase-3 were detected in SW982 cells by RT-qPCR and western blotting at various time-points (48 and 72 h) following transfection with Bcl-2-sh1, in order to observe the effectiveness of this interference. Compared with the control group, the expression levels of Bcl-2 were decreased, while those of Bax, CytC and Caspase-3 were increased in Bcl-2-sh1-transfected cells (P<0.01). The interference effect was greater at 48 h than at 72 h. In summary, an effective shRNA sequence (Bcl-2-sh1) targeting the Bcl-2 gene was identified from three candidates, and was demonstrated to significantly interfere with the expression of Bcl-2, Bax, CytC and Caspase-3 when transfected into SW982 cells. The interference effect of Bcl-2-sh1 was more pronounced at 48 h than at 72 h post-transfection.

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“…1 AFB1 exposure induces a decrease in L02 cell viability, oxidative stress, and apoptosis. a L02 cells were untreated (Ctrl) or treated with increasing concentrations of AFB1 (5,10,20,40,80, and 160 μM) for 24 h or with 40 μM AFB1 for the indicated time points (12,24,36,48,60, and 72 h); the cell viability was then detected by CCK-8 assay. b L02 cells were untreated (Ctrl) or treated with 40 μM AFB1 for 36 h. ROS production was detected by DCF probe staining and the percentage of DCF-positive hepatocytes was processed and quantified using ImageJ software (scale bar = 200 μm).…”

Section: Cav-1 Plays An Important Role In the Regulation Of Afb1inducmentioning

confidence: 99%

“…AFB1 can impair the antioxidant/prooxidant imbalance and elevate lipid peroxidation, resulting in the damage of biological molecules including lipids, proteins, and DNA in cellular systems 8 . The combination of these effects leads to the activation of a programmed cell death process or induces cells to produce potentially catastrophic genetic alterations, which depend on the dose and duration of AFB1 exposure 9,10 . A growing body of evidence has demonstrated that the detoxification of this toxin can generally be mediated by antioxidants, such as heme oxygenase-1 (HO-1), NAD(P)H/quinone oxidoreductase-1 (NQO1), and glutathione S-transferases (GSH), indicating the importance of oxidative stress regulation in AFB1induced hepatotoxicity 11 .…”

Section: Introductionmentioning

confidence: 99%

Critical role of caveolin-1 in aflatoxin B1-induced hepatotoxicity via the regulation of oxidation and autophagy

Xu¹,

Shi²,

Lv³

et al. 2020

Cell Death Dis

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Aflatoxin B1 (AFB1) is a potent hepatocarcinogen in humans and exposure to AFB1 is known to cause both acute and chronic hepatocellular injury. As the liver is known to be the main target organ of aflatoxin, it is important to identify the key molecules that participate in AFB1-induced hepatotoxicity and to investigate their underlying mechanisms. In this study, the critical role of caveolin-1 in AFB1-induced hepatic cell apoptosis was examined. We found a decrease in cell viability and an increase in oxidation and apoptosis in human hepatocyte L02 cells after AFB1 exposure. In addition, the intracellular expression of caveolin-1 was increased in response to AFB1 treatment. Downregulation of caveolin-1 significantly alleviated AFB1-induced apoptosis and decreased cell viability, whereas overexpression of caveolin-1 reversed these effects. Further functional analysis showed that caveolin-1 participates in AFB1-induced oxidative stress through its interaction with Nrf2, leading to the downregulation of cellular antioxidant enzymes and the promotion of oxidative stress-induced apoptosis. In addition, caveolin-1 was found to regulate AFB1-induced autophagy. This finding was supported by the effect that caveolin-1 deficiency promoted autophagy after AFB1 treatment, leading to the inhibition of apoptosis, whereas overexpression of caveolin-1 inhibited autophagy and accelerated apoptosis. Interestingly, further investigation showed that caveolin-1 participates in AFB1-induced autophagy by regulating the EGFR/PI3K-AKT/mTOR signaling pathway. Taken together, our data reveal that caveolin-1 plays a crucial role in AFB1-induced hepatic cell apoptosis via the regulation of oxidation and autophagy, which provides a potential target for the development of novel treatments to combat AFB1 hepatotoxicity.

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The mitochondrial and endoplasmic reticulum pathways involved in the apoptosis of bursa of Fabricius cells in broilers exposed to dietary aflatoxin B1

Cited by 42 publications

References 46 publications

Subchronic arsenism-induced oxidative stress and inflammation contribute to apoptosis through mitochondrial and death receptor dependent pathways in chicken immune organs

Subchronic arsenism-induced oxidative stress and inflammation contribute to apoptosis through mitochondrial and death receptor dependent pathways in chicken immune organs

Construction of a Bcl-2-shRNA expression vector and its effect on the mitochondrial apoptosis pathway in SW982 cells

Critical role of caveolin-1 in aflatoxin B1-induced hepatotoxicity via the regulation of oxidation and autophagy

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