Activation of pyroptosis and ferroptosis is involved in radiation-induced intestinal injury in mice

Zhang, Feng; Li, Teng; Huang, Hua-cui; Zhao, Yangyang; He, Miao; Yuan, Wei; Li, Li; Li, Jin; Wu, Dongming; Xu, Ying

doi:10.1016/j.bbrc.2022.09.073

Cited by 14 publications

(14 citation statements)

References 27 publications

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“…NLRC4 can directly interact with caspase-1 when overexpressed [ 60 ]. Pyroptosis is found to be involved in dysfunction of intestinal injury [ 61 ]. In the present study, consistent with necroptosis, we found that PCA or Que decreased protein level of NLRP3, ASC, NLRC4, caspase-1 and IL-18 after ETEC K88 infection, suggesting a protective role on inhibiting pyroptosis signaling pathway activation.…”

Section: Discussionmentioning

confidence: 99%

Protocatechuic acid and quercetin attenuate ETEC-caused IPEC-1 cell inflammation and injury associated with inhibition of necroptosis and pyroptosis signaling pathways

Xiao

Zhou

et al. 2023

J Animal Sci Biotechnol

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Background Necroptosis and pyroptosis are newly identified forms of programmed cell death, which play a vital role in development of many gastrointestinal disorders. Although plant polyphenols have been reported to protect intestinal health, it is still unclear whether there is a beneficial role of plant polyphenols in modulating necroptosis and pyroptosis in intestinal porcine epithelial cell line (IPEC-1) infected with enterotoxigenic Escherichia coli (ETEC) K88. This research was conducted to explore whether plant polyphenols including protocatechuic acid (PCA) and quercetin (Que), attenuated inflammation and injury of IPEC-1 caused by ETEC K88 through regulating necroptosis and pyroptosis signaling pathways. Methods IPEC-1 cells were treated with PCA (40 μmol/L) or Que (10 μmol/L) in the presence or absence of ETEC K88. Results PCA and Que decreased ETEC K88 adhesion and endotoxin level (P < 0.05) in cell supernatant. PCA and Que increased cell number (P < 0.001) and decreased lactate dehydrogenases (LDH) activity (P < 0.05) in cell supernatant after ETEC infection. PCA and Que improved transepithelial electrical resistance (TEER) (P < 0.001) and reduced fluorescein isothiocyanate-labeled dextran (FD4) flux (P < 0.001), and enhanced membrane protein abundance of occludin, claudin-1 and ZO-1 (P < 0.05), and rescued distribution of these tight junction proteins (P < 0.05) after ETEC infection. PCA and Que also declined cell necrosis ratio (P < 0.05). PCA and Que reduced mRNA abundance and concentration of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-8 (P < 0.001), and down-regulated gene expression of toll-like receptors 4 (TLR4) and its downstream signals (P < 0.001) after ETEC infection. PCA and Que down-regulated protein abundance of total receptor interacting protein kinase 1 (t-RIP1), phosphorylated-RIP1 (p-RIP1), p-RIP1/t-RIP1, t-RIP3, p-RIP3, mixed lineage kinase domain-like protein (MLKL), p-MLKL, dynamin- related protein 1 (DRP1), phosphoglycerate mutase 5 (PGAM5) and high mobility group box 1 (HMGB1) (P < 0.05) after ETEC infection. Moreover, PCA and Que reduced protein abundance of nod-like receptor protein 3 (NLRP3), nod-like receptors family CARD domain-containing protein 4 (NLRC4), apoptosis-associated speck-like protein containing a CARD (ASC), gasdermin D (GSDMD) and caspase-1 (P < 0.05) after ETEC infection. Conclusions In general, our data suggest that PCA and Que are capable of attenuating ETEC-caused intestinal inflammation and damage via inhibiting necroptosis and pyroptosis signaling pathways.

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Section: Discussionmentioning

confidence: 99%

Protocatechuic acid and quercetin attenuate ETEC-caused IPEC-1 cell inflammation and injury associated with inhibition of necroptosis and pyroptosis signaling pathways

Xiao

Zhou

et al. 2023

J Animal Sci Biotechnol

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“…The destruction of RBCs results in reduced tissue oxygenation and the release of iron, likely contributing to subsequent organ sequelae (14)(15)(16)(17)(18)(19). Using murine models of H-ARS, our laboratory and others demonstrated increased iron deposition in several tissues, including bone marrow, spleen, heart, and intestines at 1-2 weeks postirradiation (16)(17)(18)(19)(20)(21). Direct iron assays and/ or histological evaluation of the tissue revealed iron increased » tenfold in the bone marrow and .sixfold in the spleen (16,17).…”

Section: Introductionmentioning

confidence: 94%

“…However, reticulocytes and red blood cells (RBCs) lack DNA and apoptotic machinery, and these cells instead undergo hemolysis following radiation exposure ( 6 , 12 – 14 ). The destruction of RBCs results in reduced tissue oxygenation and the release of iron, likely contributing to subsequent organ sequelae ( 14 – 19 ). Using murine models of H-ARS, our laboratory and others demonstrated increased iron deposition in several tissues, including bone marrow, spleen, heart, and intestines at 1–2 weeks postirradiation ( 16 – 21 ).…”

Section: Introductionmentioning

confidence: 99%

Iron Deposition in the Bone Marrow and Spleen of Nonhuman Primates with Acute Radiation Syndrome

Day,

Rittase,

Slaven

et al. 2023

Radiation Research

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The risk of exposure to high levels of ionizing radiation from nuclear weapons or radiological accidents is an increasing world concern. Partial- or total-body exposure to high doses of radiation is potentially lethal through the induction of acute radiation syndrome (ARS). Hematopoietic cells are sensitive to radiation exposure; white blood cells primarily undergo apoptosis while red blood cells (RBCs) undergo hemolysis. Several laboratories demonstrated that the rapid hemolysis of RBCs results in the release of acellular iron into the blood. We recently demonstrated using a murine model of ARS after total-body irradiation (TBI) and the loss of RBCs, iron accumulated in the bone marrow and spleen, notably between 4–21 days postirradiation. Here, we investigated iron accumulation in the bone marrow and spleens from TBI nonhuman primates (NHPs) using histological stains. We observed trends in increased intracellular and extracellular brown pigmentation in the bone marrow after various doses of radiation, especially after 4–15 days postirradiation, but these differences did not reach significance. We observed a significant increase in Prussian blue-staining intracellular iron deposition in the spleen 13–15 days after 5.8–8.5 Gy of TBI. We observed trends of increased iron in the spleen after 30–60 days postirradiation, with varying doses of radiation, but these differences did not reach significance. The NHP model of ARS confirms our earlier findings in the murine model, showing iron deposition in the bone marrow and spleen after TBI.

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“…Zhang et al demonstrated that the caspase-1 inhibitor VX-765 (Figure 2 G) and the ferroptosis inhibitor ferrostatin-1 hindered pyroptosis and ferroptosis, respectively. PDTC could simultaneously reverse indicators of pyroptosis and ferroptosis by inhibiting NF-κB (Figure 2 H) 102 . Overall, inhibiting NF-κB can suppress radiation-induced pyroptosis and mitigate radiation injury.…”

Section: Introductionmentioning

confidence: 98%

“…Numerous studies proved that the NF-κB pathway contributes to the development of pyroptosis 100 , 101 . Commonly used NF-κB inhibitors include andrographolide 97 , human recombinant manganese superoxide dismutase (rMnSOD) 74 , micheliolide 92 , p-Coumaric acid 79 , and pyrrolidinedithiocarbamate ammonium (PDTC) 102 . Pre-administration of these inhibitors followed by irradiation effectively reduces cell pyroptosis and the release of pro-inflammatory factors, thereby mitigating radiation injury.…”

Section: Introductionmentioning

confidence: 99%

The scheme, and regulative mechanism of pyroptosis, ferroptosis, and necroptosis in radiation injury

Ning,

Chen,

Zeng

et al. 2024

Int. J. Biol. Sci.

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Radiotherapy (RT) stands as the primary treatment for tumors, but it inevitably causes damage to normal cells. Consequently, radiation injury is a crucial consideration for radiation oncologists during therapy planning. Cell death including apoptosis, autophagy, pyroptosis, ferroptosis, and necroptosis play significant roles in tumor treatment. While previous studies elucidated the induction of apoptosis and autophagy by ionizing radiation (IR), recent attention has shifted to pyroptosis, ferroptosis, and necroptosis, revealing their effects induced by IR. This review aims to summarize the strategies employed by IR, either alone or in combination therapy, to induce pyroptosis, ferroptosis, and necroptosis in radiation injury. Furthermore, we explore their effects and molecular pathways, shedding light on their roles in radiation injury. Finally, we summarize the regulative agents for these three types of cell death and their mechanisms. In summary, optimizing radiation dose, dose rate, and combined treatment plans to minimize radiation damage and enhance the killing effect of RT is a key focus.

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Activation of pyroptosis and ferroptosis is involved in radiation-induced intestinal injury in mice

Cited by 14 publications

References 27 publications

Protocatechuic acid and quercetin attenuate ETEC-caused IPEC-1 cell inflammation and injury associated with inhibition of necroptosis and pyroptosis signaling pathways

Protocatechuic acid and quercetin attenuate ETEC-caused IPEC-1 cell inflammation and injury associated with inhibition of necroptosis and pyroptosis signaling pathways

Iron Deposition in the Bone Marrow and Spleen of Nonhuman Primates with Acute Radiation Syndrome

The scheme, and regulative mechanism of pyroptosis, ferroptosis, and necroptosis in radiation injury

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