Endoplasmic Reticulum Stress Contributes to Copper-Induced Pyroptosis <i>via</i> Regulating the IRE1α-XBP1 Pathway in Pig Jejunal Epithelial Cells

Liao, Jianzhao; Hu, Zhuoying; Li, Quanwei; Li, Hongji; Chen, Weijin; Huo, Haihua; Han, Qing; Zhang, Hui; Guo, Jianying; Hu, Lianmei; Pan, Jiang; Liu, Ying; Tang, Zhaoxin

doi:10.1021/acs.jafc.1c07927

Cited by 46 publications

(28 citation statements)

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“…Our previous findings demonstrated that the copper contents was found to be significant accumulated in hindgut digesta with increased dietary copper levels in rats and piglets, the accumulation of copper alters the composition of intestinal microbiota in both animals 8 , 15 . More importantly, a significant correlation between the alterations of intestinal microbiota and serum TNF-α concentration was observed in rat experiments, which suggested that TNF-α could be the chief responder to microbiota shift under excessive copper exposure 1 . Otherwise, the correlation analysis of microbiome-metabolome suggested that dietary high-level copper alter the composition of the gut microbiota and modulate microbial metabolic pathways, which may further affect the health of suckling piglets 2 .…”

Section: Introductionmentioning

confidence: 88%

“…Significantly changed Na, K, Mg, Mn and Cu concentrations in hair can reflect the adverse effects of dietary 300 mg•kg −1 copper of suckling piglets. We believe our results may benefit people to gain a better understanding of the ion interactions and metabolic homeostasis of heavy metal elements that are critical to human and animal health.Copper is a crucial trace element for the normal and healthy growth of mammals [1][2][3][4][5] . It has been found that at higher concentrations, copper exposure has been linked to liver disease, neurological disorders, reproductive abnormalities, and a multitude of other detrimental impacts on humans and animals 3,6 .…”

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confidence: 99%

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Ionomics-metabolome association analysis as a new approach to the impact of dietary copper levels in suckling piglets model

Zhang

Yao

et al. 2023

Sci Rep

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Ionomics-metabolomics association analysis is a novel method to elucidating the potential mechanisms underlying the effects of dietary copper on the overall health parameters of suckling piglets model. Few studies have elucidated the relationship between the changes of ionic and metabolic homeostasis responses to dietary copper level. The growth performance data was obtained from 180 suckling piglets which access to different copper levels: 6 (low copper diet, LC), 20 (control diet, CON), and 300 (high copper diet, HC) mg·kg−1 copper (based on diet, supplementation from CuSO4), and offered ad libitum from d 14 until weaning at 40 d of age. Dietary high level copper (300 mg·kg−1) increased the ADG and ADFI during d 14 to 28 of piglets. Six elements (Mg, Na, K, P, Cu, and Mn) concentrations significantly changes in hair among the three treatment diets. The significant increased concentrations of Na and K, and decreased concentration of Mg and Mn in 300 mg·kg−1 than 20 mg·kg−1 copper diet was observed. In current study, with the increase in copper level from 20 to 300 mg·kg−1 in diet, the correlation between hair Na, K and Cu, Mn, Zn vanish. Hair Na and K were positively correlated with serum total antioxidant capacity (T-AOC) and negatively correlated with tumor necrosis factor-α (TNF-α). The hair Cu was negatively correlated with serum malondialdehyde (MDA), total bile acid (TBA). The fecal Cu was positively correlated with serum growth hormone (GH). The results suggested that the average daily gain (ADG) in 6 mg·kg−1 copper diet and the average daily feed intake (ADFI) in 20 mg·kg−1 copper diet were decreased than 300 mg·kg−1 copper diet during d 14 to 28 and the ADG was decreased in 6 and 20 mg·kg−1 copper diets in d 29 to 40 of piglets. Dietary 20 mg·kg−1 copper maintain ion homeostasis due to increase the number of positive correlations between macroelements-microelements in hair and serum. Significantly changed Na, K, Mg, Mn and Cu concentrations in hair can reflect the adverse effects of dietary 300 mg·kg−1 copper of suckling piglets. We believe our results may benefit people to gain a better understanding of the ion interactions and metabolic homeostasis of heavy metal elements that are critical to human and animal health.

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Section: Introductionmentioning

confidence: 88%

mentioning

confidence: 99%

Ionomics-metabolome association analysis as a new approach to the impact of dietary copper levels in suckling piglets model

Zhang

Yao

et al. 2023

Sci Rep

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“…Another study reported that excessive intake of Cu 2+ can cause ER expansion, increase the expression of GRP78 and caspase1 proteins, and increase the expression of ERS and pyroptosis-related proteins and mRNAs, indicating that Cu 2+ can cause pyroptosis through ERS. In addition, they found that both 4-Phenylbutyric acid (4-PBA, ERS inhibitor) and MKC-394 (IRE1α inhibitor) could inhibit ERS to alleviate the occurrence of pyroptosis [ 55 ]. These results suggest that ERS regulates copper ion-induced pyroptosis through the IRE1α-XBP1 pathway (Fig.…”

Section: Cell Death Mediated By Ers and Uprmentioning

confidence: 99%

Endoplasmic reticulum stress-mediated cell death in liver injury

et al. 2022

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The endoplasmic reticulum is an important intracellular organelle that plays an important role in maintaining cellular homeostasis. Endoplasmic reticulum stress (ERS) and unfolded protein response (UPR) are induced when the body is exposed to adverse external stimuli. It has been established that ERS can induce different cell death modes, including autophagy, apoptosis, ferroptosis, and pyroptosis, through three major transmembrane receptors on the ER membrane, including inositol requirement enzyme 1α, protein kinase-like endoplasmic reticulum kinase and activating transcription factor 6. These different modes of cell death play an important role in the occurrence and development of various diseases, such as neurodegenerative diseases, inflammation, metabolic diseases, and liver injury. As the largest metabolic organ, the liver is rich in enzymes, carries out different functions such as metabolism and secretion, and is the body’s main site of protein synthesis. Accordingly, a well-developed endoplasmic reticulum system is present in hepatocytes to help the liver perform its physiological functions. Current evidence suggests that ERS is closely related to different stages of liver injury, and the death of hepatocytes caused by ERS may be key in liver injury. In addition, an increasing body of evidence suggests that modulating ERS has great potential for treating the liver injury. This article provided a comprehensive overview of the relationship between ERS and four types of cell death. Moreover, we discussed the mechanism of ERS and UPR in different liver injuries and their potential therapeutic strategies.

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“…Excess Cu induced pyroptosis by generating ROS in hepatocytes, and the inhibition of Caspase-1-dependent pyroptosis might attenuate Cu-induced apoptosis [ 155 ]. In addition, there are research findings that ER stress also participated in regulating Cu-induced pyroptosis in jejunal epithelial cells via the IRE1 α -XBP1 pathway [ 156 ], which provided a novel view into the toxicology of copper.…”

Section: Defective Copper Metabolism and Dcmmentioning

confidence: 99%

The Molecular Mechanisms of Defective Copper Metabolism in Diabetic Cardiomyopathy

Cui

Wang

Liu

et al. 2022

Oxidative Medicine and Cellular Longevity

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Copper is an essential trace metal element that significantly affects human physiology and pathology by regulating various important biological processes, including mitochondrial oxidative phosphorylation, connective tissue crosslinking, and antioxidant defense. Copper level has been proved to be closely related to the morbidity and mortality of cardiovascular diseases such as atherosclerosis, heart failure, and diabetic cardiomyopathy (DCM). Copper deficiency can induce cardiac hypertrophy and aggravate cardiomyopathy, while copper excess can mediate various types of cell death, such as autophagy, apoptosis, cuproptosis, pyroptosis, and cardiac hypertrophy and fibrosis. Both copper excess and copper deficiency lead to redox imbalance, activate inflammatory response, and aggravate diabetic cardiomyopathy. This defective copper metabolism suggests a specific metabolic pattern of copper in diabetes and a specific role in the pathogenesis and progression of DCM. This review is aimed at providing a timely summary of the effects of defective copper homeostasis on DCM and discussing potential underlying molecular mechanisms.

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Endoplasmic Reticulum Stress Contributes to Copper-Induced Pyroptosis via Regulating the IRE1α-XBP1 Pathway in Pig Jejunal Epithelial Cells

Cited by 46 publications

References 50 publications

Ionomics-metabolome association analysis as a new approach to the impact of dietary copper levels in suckling piglets model

Ionomics-metabolome association analysis as a new approach to the impact of dietary copper levels in suckling piglets model

Endoplasmic reticulum stress-mediated cell death in liver injury

The Molecular Mechanisms of Defective Copper Metabolism in Diabetic Cardiomyopathy

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