Benzo[a]pyrene induces pyroptotic and autophagic death through inhibiting PI3K/Akt signaling pathway in HL-7702 human normal liver cells

Li, Qingshu; Gao, Chunxia; Deng, Hong; Song, Quancai; Li, Yuan

doi:10.2131/jts.44.121

Cited by 16 publications

(7 citation statements)

References 27 publications

(25 reference statements)

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“…It has been reported that Gossypol, Arsenic, and Cadmium induced the pyroptotic damage [13][14][15]. Our preliminary study also demonstrates that BaP caused hepatocytes damage via inducing pyroptosis [25,28]. Iso is a natural flavonoid with a luteolin structure that is widespread in some foods and edible plants [29,30].…”

Section: Discussionmentioning

confidence: 57%

Isoorientin Attenuated the Pyroptotic Hepatocyte Damage Induced by Benzo[a]pyrene via ROS/NF-κB/NLRP3/Caspase-1 Signaling Pathway

et al. 2021

Antioxidants

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Isoorientin (Iso), a natural bioactive flavonoid, possesses significant anti-tumor and anti-oxidant activities. Benzo[a]pyrene (BaP) is a food processing injurant with carcinogenicity, teratogenicity, and genotoxicity. Our preliminary study demonstrates that Iso attenuated the pyroptotic hepatocyte damage induced by BaP; however, the molecular mechanism remains unknown. The present study showed that Iso reduced the increase caused by BaP in the overflow of LDH, NO, and the electrical conductivity and the protein expressions of GSDMD-N, IL-18, and IL-1β, further showing that Iso could reduced the pyroptotic damage in HL-7702 cells induced by BaP. Caspase-1 inhibitor (Z-VAD-FMK) inhibited the characteristic pyroptosis protein expressions of Caspase-1, GSDMD-N, IL-18, and IL-1β, showing that the classic pyroptosis pathway depending on Caspase-1 was caused by BaP in HL-7702 cells. Consistent with the effects of the NLRP3 inhibitor (MCC950), NF-κB inhibitor (PDTC), ROS, and mtROS inhibitor (NAC and Mito-TEMPO), Iso weakened the stimulatory effects of BaP on the levels of ROS, the nuclear localization of NF-κB, and the activation of NLRP3 inflammasome and the characteristic indices of pyroptosis, demonstrating that Iso could alleviate the BaP-induced pyroptotic hepatocytes injury through inhibiting the ROS/NF-κB/NLRP3/Caspase-1 signaling pathway, which provides a new perspective and strategy to prevent liver injury induced by BaP.

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Section: Discussionmentioning

confidence: 57%

Isoorientin Attenuated the Pyroptotic Hepatocyte Damage Induced by Benzo[a]pyrene via ROS/NF-κB/NLRP3/Caspase-1 Signaling Pathway

et al. 2021

Antioxidants

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“…Based on these findings, we hypothesized that selenium could protect cells from apoptosis by regulating the PI3K/AKT pathway. To examine this, we incubated MC3T3-E1 cells with 20 mM of LY294002 (the inhibitor of PI3K/AKT) (Li et al, 2019). We found that selenium rescued the cells from LPS-induced apoptosis.…”

Section: Selenium Protected Cells Through Pi3k/akt/mir-155 Signaling Pathwaymentioning

confidence: 99%

Selenium protects against LPS-induced MC3T3-E1 cells apoptosis through modulation of microRNA-155 and PI3K/Akt signaling pathways

Huang

Jia

et al. 2020

Genet. Mol. Biol.

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Bone infection or osteomyelitis is usually a complication of inflammation-related traumatic bone injury. Selenium has been shown to have potential cytoprotective effects and the ability to reduce oxidative stress and apoptotic events in osteomyelitis, but the exact mechanism remains unclear. Here, we used LPS-induced apoptotic MC3T3-E1 cells and aimed to confirm selenium's protective effect on cell apoptosis as well as to investigate the underlying mechanisms of this role. Our investigation confirmed selenium-mediated inhibition of LPS-induced cell apoptosis and ROS accumulation in MC3T3-E1 cells. Upon selenium treatment, the bcl-2 levels were upregulated, while the levels of Bax and cyto-C were down-regulated. Furthermore, these effects were accompanied by the suppression of miR-155 and the phosphorylation of protein kinase B (Akt). A more in-depth study demonstrated that LY294002 (a specific inhibitor of PI3K), abolished the selenium-mediated cytoprotective effect of MC3T3-E1 cells against LPS-induced injury and down-regulation of miR-155. In general, these results demonstrated that selenium exerts a cytoprotective effect by attenuating cell apoptosis and oxidative damage via a PI3K/Akt/miR-155-dependent mechanism.

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“…Indeed, additional experiments demonstrated a dose-dependent induction of SLC13A5 by BaP through concentrations up to 100 µM. Higher concentrations of BaP at and above 20 µM have previously been indicated to be toxic to hepatocytes [68,69]. Whether BaP causes cellular toxic responses and also contributes to its upregulation of SLC13A5 remains elusive.…”

Section: Ahr In the Slc13a5 Transcriptionmentioning

confidence: 99%

Molecular Mechanisms of the SLC13A5 Gene Transcription

Li¹,

Wang²

2021

Metabolites

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Citrate is a crucial energy sensor that plays a central role in cellular metabolic homeostasis. The solute carrier family 13 member 5 (SLC13A5), a sodium-coupled citrate transporter highly expressed in the mammalian liver with relatively low levels in the testis and brain, imports citrate from extracellular spaces into the cells. The perturbation of SLC13A5 expression and/or activity is associated with non-alcoholic fatty liver disease, obesity, insulin resistance, cell proliferation, and early infantile epileptic encephalopathy. SLC13A5 has been proposed as a promising therapeutic target for the treatment of these metabolic disorders. In the liver, the inductive expression of SLC13A5 has been linked to several xenobiotic receptors such as the pregnane X receptor and the aryl hydrocarbon receptor as well as certain hormonal and nutritional stimuli. Nevertheless, in comparison to the heightened interest in understanding the biological function and clinical relevance of SLC13A5, studies focusing on the regulatory mechanisms of SLC13A5 expression are relatively limited. In this review, we discuss the current advances in our understanding of the molecular mechanisms by which the expression of SLC13A5 is regulated. We expect this review will provide greater insights into the regulation of the SLC13A5 gene transcription and the signaling pathways involved therein.

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Benzo[a]pyrene induces pyroptotic and autophagic death through inhibiting PI3K/Akt signaling pathway in HL-7702 human normal liver cells

Cited by 16 publications

References 27 publications

Isoorientin Attenuated the Pyroptotic Hepatocyte Damage Induced by Benzo[a]pyrene via ROS/NF-κB/NLRP3/Caspase-1 Signaling Pathway

Isoorientin Attenuated the Pyroptotic Hepatocyte Damage Induced by Benzo[a]pyrene via ROS/NF-κB/NLRP3/Caspase-1 Signaling Pathway

Selenium protects against LPS-induced MC3T3-E1 cells apoptosis through modulation of microRNA-155 and PI3K/Akt signaling pathways

Molecular Mechanisms of the SLC13A5 Gene Transcription

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