Copper sulfate-induced endoplasmic reticulum stress promotes hepatic apoptosis by activating CHOP, JNK and caspase-12 signaling pathways

Wu, H. C.; Guo, Hongrui; Liu, Huan; Cui, Hengmin; Fang, Jing; Zuo, Zhuang; Deng, Junliang; Li, Yinglun; Wang, Xun; Zhao, Ling

doi:10.1016/j.ecoenv.2020.110236

Cited by 74 publications

(28 citation statements)

References 52 publications

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“…In some countries, copper sulfate (CuSO 4 ) has been widely used as a feed additive in animal production (2). However, copper overload could cause the tissue or organ damage in human and other mammals, affecting the liver, kidney, brain, lung, intestine, heart, and testis (3)(4)(5)(6)(7)(8)(9)(10). Over the past decades, Cu overload was suggested to be associated with the development of Wilson's disease and other neurodegenerative diseases, which has raised concerns worldwide (7,11).…”

Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

et al. 2021

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Copper overload is an established cause of nephrotoxicity, but the precise molecular mechanism remains unknown. Our study aimed to investigate the molecular mechanism of copper sulfate (CuSO4)-induced nephrotoxicity and the protective effect of the natural compound quercetin using a mouse model. Mice were orally administered CuSO4 only (200 mg/kg per day), or co-administered CuSO4 (200 mg/kg per day) plus quercetin (25, 50, or 100 mg/kg per day), or quercetin only (100 mg/kg per day), or vehicle for 28 days. The blood and kidneys were collected for the examination of serum biomarkers, oxidative stress biomarkers, changes in histopathology and gene and protein expression. Our results show that quercetin supplementation attenuates CuSO4-induced renal dysfunction and tubular necrosis in a dose-dependent manner. Quercetin supplementation at 50 and 100 mg/kg significantly attenuated CuSO4-induced oxidative damage. Quercetin supplementation also inhibited the activities of caspases-9 and−3, and the expression of p53 and Bax mRNAs. Furthermore, quercetin supplementation markedly activated the expression of Nrf2 and HO-1 mRNAs, but inhibited the expression of NF-κB, IL-1β, IL-6, and TNF-α mRNAs. In conclusion, our results revealed that quercetin supplementation could inhibit CuSO4-induced nephrotoxicity in mice via the inhibition of mitochondrial apoptotic and NF-κB pathways and the activation of Nrf2/HO-1 pathway. Our study highlights quercetin as a potential candidate in treating copper overload-induced nephrotoxicity.

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Section: Introductionmentioning

confidence: 99%

Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

et al. 2021

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“…The pro-apoptotic factor CHOP and caspase-12 are induced, then ultimately induce cell death through its downstream effectors, caspases-9 or -3 [ 20 , 50 ]. A recent study reported that ER stress in a mouse model was associated with CuSO 4 -induced liver damage and increased levels of GRP78, GRP94, PERK, IRE1, ATF6, ATF4, CHOP, caspase-12 mRNAs and proteins [ 8 ]. In the present study, after mice were administered orally with CuSO 4 at 50–200 mg/kg/day for 28 days, the mRNA levels of GRP78, GRP94, CHOP, and caspase-12 significantly increased ( Figure 6 ).…”

Section: Discussionmentioning

confidence: 99%

“…The excess free Cu is redox-active and catalyzes the production of hydroxyl radicals in a Cu-dependent ‘Fenton-like’ reaction, then triggering oxidative stress and damaging cells or tissues [ 1 ]. It has been reported that the high dose of Cu exposure can damage various tissues and organs, including the kidney, brain, liver, intestines, and testis [ 5 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ]. In particular, the kidney is vulnerable to toxic effects from Cu due to its filtration functions.…”

Section: Introductionmentioning

confidence: 99%

“…Endoplasmic reticulum (ER) is an important organelle that plays a vital role in storing calcium, synthesizing proteins and detoxifying harmful substances [ 19 ]. ER stress-mediated apoptosis was detected in mouse liver tissue exposure to CuSO 4 [ 8 ]. The previous studies have demonstrated that ER stress is affected by some drugs (e.g., colistin and cisplatin), toxins (e.g., zearalenone) and heavy metals (e.g., lead and cadmium)-induced renal damage in vitro and animal models [ 20 , 21 , 22 , 23 , 24 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

“…The previous studies have demonstrated that ER stress is affected by some drugs (e.g., colistin and cisplatin), toxins (e.g., zearalenone) and heavy metals (e.g., lead and cadmium)-induced renal damage in vitro and animal models [ 20 , 21 , 22 , 23 , 24 , 25 ]. ER stress-mediated apoptosis was observed in mouse liver tissues and involved the activation of growth arrest- and DNA damage-inducible gene 153 (GADD153/CHOP), c-Jun N-terminal kinase (JNK) and caspase-12 signaling pathways [ 8 ]. Up until now, the ER stress contribution in CuSO 4 exposure-induced nephrotoxicity remains poorly understood.…”

Section: Introductionmentioning

confidence: 99%

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Molecular Insights of Copper Sulfate Exposure-Induced Nephrotoxicity: Involvement of Oxidative and Endoplasmic Reticulum Stress Pathways

Dai

Liu

et al. 2020

Biomolecules

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The precise pathogenic mechanism in Cu exposure-cause nephrotoxicity remains unclear. This study investigated the underlying molecular mechanism of copper sulfate (CuSO4)-induced nephrotoxicity. Mice were treated with CuSO4 at 50, 100, 200 mg/kg/day or co-treated with CuSO4 (200 mg/kg/day) and 4-phenylbutyric acid (4-PBA, 100 mg/kg/day) for 28 consecutive days. HEK293 cells were treated with CuSO4 (400 μM) with or without superoxide dismutase, catalase or 4-PBA for 24 h. Results showed that CuSO4 exposure can cause renal dysfunction and tubular necrosis in the kidney tissues of mice. CuSO4 exposure up-regulated the activities and mRNA expression of caspases-9 and -3 as well as the expression of glucose-regulated protein 78 (GRP78), GRP94, DNA damage-inducible gene 153 (GADD153/CHOP), caspase-12 mRNAs in the kidney tissues. Furthermore, superoxide dismutase and catalase pre-treatments partly inhibited CuSO4-induced cytotoxicity by decreasing reactive oxygen species (ROS) production, activities of caspases-9 and -3 and DNA fragmentations in HEK293 cells. 4-PBA co-treatment significantly improved CuSO4-induced cytotoxicity in HEK293 cells and inhibited CuSO4 exposure-induced renal dysfunction and pathology damage in the kidney tissues. In conclusion, our results reveal that oxidative stress and endoplasmic reticulum stress contribute to CuSO4-induced nephrotoxicity. Our study highlights that targeting endoplasmic reticulum and oxidative stress may offer an approach for Cu overload-caused nephrotoxicity.

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Interrelation between Programmed Cell Death and Immunogenic Cell Death: Take Antitumor Nanodrug as an Example

Meng

Ding

et al. 2023

Small Methods

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Programmed cell death (PCD, mainly including apoptosis, necrosis, ferroptosis, pyroptosis, and autophagy) and immunogenic cell death (ICD), as important cell death mechanisms, are widely reported in cancer therapy, and understanding the relationship between the two is significant for clinical tumor treatments. Considering that vast nanodrugs are developed to induce tumor PCD and ICD simultaneously, in this review, the interrelationship between PCD and ICD is described using nanomedicines as examples. First, an overview of PCD patterns and focus on the morphological differences and interconnections among them are provided. Then the interrelationship between apoptosis and ICD in terms of endoplasmic reticulum stress is described by introducing various cancer treatments and the recent developments of nanomedicines with inducible immunogenicity. Next, the crosstalk between non‐apoptotic (including necrosis, ferroptosis, pyroptosis, and autophagy) signaling pathways and ICD is introduced and their relationship through various nanomedicines as examples is further illustrated. Finally, the relationship between PCD and ICD and its application prospects in the development of new ICD nanomaterials are summarized. This review is believed to deepen the understanding of the relationship between PCD and ICD, extend the biomedical applications of various nanodrugs, and promote the progress of clinical tumor therapy.

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Copper sulfate-induced endoplasmic reticulum stress promotes hepatic apoptosis by activating CHOP, JNK and caspase-12 signaling pathways

Cited by 74 publications

References 52 publications

Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

Molecular Mechanisms Underlying Protective Role of Quercetin on Copper Sulfate-Induced Nephrotoxicity in Mice

Molecular Insights of Copper Sulfate Exposure-Induced Nephrotoxicity: Involvement of Oxidative and Endoplasmic Reticulum Stress Pathways

Interrelation between Programmed Cell Death and Immunogenic Cell Death: Take Antitumor Nanodrug as an Example

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