Deoxynivalenol induces caspase-3/GSDME-dependent pyroptosis and inflammation in mouse liver and HepaRG cells

Mao, Xiaodan; Li, Jie; Xie, Xing; Chen, Shuang; Huang, Qiang; Mu, Peiqiang; Jiang, Jun; Deng, Yiqun

doi:10.1007/s00204-022-03344-9

Cited by 20 publications

(7 citation statements)

References 67 publications

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“…Compound lidocaine cream was topically administered for postoperative analgesia. Caspase-3-specific inhibitor Ac-DC (4 μg/g) 51 (Apexbio, Houston, TX, USA) was dissolved in saline and injected intraperitoneally once daily for 3 d after surgery. Control (sham-treated) rats received 100% oxygen without surgery or anesthesia.…”

Section: ■ Experimental Methodsmentioning

confidence: 99%

Inhibition of PINK1-Mediated Mitophagy Contributes to Postoperative Cognitive Dysfunction through Activation of Caspase-3/GSDME-Dependent Pyroptosis

Wang

Zhao

Gao

et al. 2023

ACS Chem. Neurosci.

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PTEN-induced kinase 1 (PINK1)-mediated mitophagy and caspase-1/gasdermin D canonical pyroptosis pathways have been implicated in the pathogenesis of postoperative cognitive dysfunction (POCD). However, gasdermin E (GSDME), another recently identified executioner of pyroptosis that can be specifically cleaved by caspase-3, is highly expressed in the brain and neurons. This study aimed to ascertain whether PINK1-dependent mitophagy governs postoperative cognitive capacity through caspase-3/GSDME. Twelve month old male Sprague-Dawley rats underwent exploratory laparotomy under isoflurane anesthesia. Lipopolysaccharide (LPS)-primed SH-SY5Y cells were used to mimic postsurgical neuroinflammation. For the interventional study, rats were administered with adeno-associated virus serotype 9 (AAV9)-mediated silencing of Pink1 and/or caspase-3 inhibitor Ac-DEVD-CHO (Ac-DC). SH-SY5Y cells were treated with siPINK1 and/or Ac-DC. Cognitive performance was assessed using the Morris water maze test. The mitophagy-and pyroptosis-related parameters were determined in the hippocampus and SH-SY5Y cells. Anesthesia/surgery and LPS caused defective PINK1-mediated mitophagy and activation of caspase-3/GSDME-dependent pyroptosis. AAV-9 mediated Pink1 overexpression mitigated cognitive impairment and caspase-3/ GSDME-dependent pyroptosis. Conversely, inhibition of PINK1 aggravates POCD and overactivates neuronal pyroptosis. These abnormalities were rescued by Ac-DC treatment. Collectively, PINK1-mediated mitophagy regulates anesthesia and surgery-induced cognitive impairment by negatively affecting the caspase-3/GSDME pyroptosis pathway, which provides a promising therapeutic target for POCD.

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Section: ■ Experimental Methodsmentioning

confidence: 99%

Inhibition of PINK1-Mediated Mitophagy Contributes to Postoperative Cognitive Dysfunction through Activation of Caspase-3/GSDME-Dependent Pyroptosis

Wang

Zhao

Gao

et al. 2023

ACS Chem. Neurosci.

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“…The liver is responsible for the detoxification of DON and its conversion to less toxic DON‐GlcA in humans and animals (Figure 2). The liver is the most vital metabolic and detoxification organ in human and animal bodies, and the majority of mycotoxins can damage the liver and cause hepatotoxicity (Mao et al., 2022). Recent studies have proven that DON induces liver injury in pigs, mice, and other animals, such as driving hepatic steatosis by lipid mobilization from adipose tissues induced by DON intoxication, causing liver fibrosis and inflammation (Figure 2) (Barbouche et al., 2020; Mao et al., 2022; Skiepko et al., 2020).…”

Section: Global Occurrence and Hazard Of Donmentioning

confidence: 99%

“…The liver is the most vital metabolic and detoxification organ in human and animal bodies, and the majority of mycotoxins can damage the liver and cause hepatotoxicity (Mao et al., 2022). Recent studies have proven that DON induces liver injury in pigs, mice, and other animals, such as driving hepatic steatosis by lipid mobilization from adipose tissues induced by DON intoxication, causing liver fibrosis and inflammation (Figure 2) (Barbouche et al., 2020; Mao et al., 2022; Skiepko et al., 2020). And beyond that, DON can induce cellular oxidative stress, apoptosis, and autophagy, and the mechanism of hepatotoxicity is oxidative stress (Nrf2/HO‐1), which contributes to liver injury transcription factor activation, inflammation, and apoptosis (Figure 2) (Ruan et al., 2022).…”

Section: Global Occurrence and Hazard Of Donmentioning

confidence: 99%

Global distribution, toxicity to humans and animals, biodegradation, and nutritional mitigation of deoxynivalenol: A review

Liu

Cai

et al. 2023

Comp Rev Food Sci Food Safe

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Deoxynivalenol (DON) is one of the main types of B trichothecenes, and it causes health‐related issues in humans and animals and imposes considerable challenges to food and feed safety globally each year. This review investigates the global hazards of DON, describes the occurrence of DON in food and feed in different countries, and systematically uncovers the mechanisms of the various toxic effects of DON. For DON pollution, many treatments have been reported on the degradation of DON, and each of the treatments has different degradation efficacies and degrades DON by a distinct mechanism. These treatments include physical, chemical, and biological methods and mitigation strategies. Biodegradation methods include microorganisms, enzymes, and biological antifungal agents, which are of great research significance in food processing because of their high efficiency, low environmental hazards, and drug resistance. And we also reviewed the mechanisms of biodegradation methods of DON, the adsorption and antagonism effects of microorganisms, and the different chemical transformation mechanisms of enzymes. Moreover, nutritional mitigation including common nutrients (amino acids, fatty acids, vitamins, and microelements) and plant extracts was discussed in this review, and the mitigation mechanism of DON toxicity was elaborated from the biochemical point of view. These findings help explore various approaches to achieve the best efficiency and applicability, overcome DON pollution worldwide, ensure the sustainability and safety of food processing, and explore potential therapeutic options with the ability to reduce the deleterious effects of DON in humans and animals.

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“…After chronic and subacute oral administration of deoxynivalenol (DON), mice liver manifested inflammatory damage, focal steatosis, focal fibrosis and activated caspase-3 as well as GSDME, which were suppressed by the caspase-3 inhibitor Z-DEVD and Ac-DEVD [75]. In vitro, typical pyroptotic characteristics and balloon-like bubbling were observed in HepaRG cells induced by DON, with activation of caspase-3 and GSDME and secretion of IL-1β [75]; knocking down GSDME and inhibiting caspases activity significantly blocked DON-induced pyroptotic characteristics, while over-expressed GSDME played a promoting role [75]. Therefore, it has been established that DON induces caspase-3/GSDME-dependent hepatocyte pyroptosis and its role in DON-induced liver inflammatory injury.…”

Section: Gsdms and Fldmentioning

confidence: 99%

Research Progress of Pyroptosis in Fatty Liver Disease

Li,

Xue,

Wei

et al. 2023

IJMS

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Fatty liver disease (FLD) is a clinical and pathological syndrome characterized by excessive fat deposition and even steatosis in hepatocytes. It has been proven that liver inflammation induced by fat and its derivatives are involved in the pathogenesis of FLD, while the precise mechanism still remains poorly understood. Pyroptosis is programmed inflammatory cell death driving cell swelling and membrane rupture. Pyroptosis is initiated by the activation of inflammasomes and caspases, which further cleaves and activates various gasdermins, leading to pores forming on the cell membrane and the release of pro-inflammatory factors such as interleukin (IL)-1β and IL-18. Recent studies demonstrate that pyroptosis occurs in hepatocytes, and inhibiting pyroptosis could effectively reduce fat deposition in the liver and could ameliorate inflammation from FLD, attracting our prime focus on the role of pyroptosis in FLD. In this manuscript, we reviewed the current understanding of pyroptosis in FLD development, aiming to provide new insights and potential research targets for the clinical diagnosis and intervention of FLD.

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Deoxynivalenol induces caspase-3/GSDME-dependent pyroptosis and inflammation in mouse liver and HepaRG cells

Cited by 20 publications

References 67 publications

Inhibition of PINK1-Mediated Mitophagy Contributes to Postoperative Cognitive Dysfunction through Activation of Caspase-3/GSDME-Dependent Pyroptosis

Inhibition of PINK1-Mediated Mitophagy Contributes to Postoperative Cognitive Dysfunction through Activation of Caspase-3/GSDME-Dependent Pyroptosis

Global distribution, toxicity to humans and animals, biodegradation, and nutritional mitigation of deoxynivalenol: A review

Research Progress of Pyroptosis in Fatty Liver Disease

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