Monobutyl phthalate can induce autophagy and metabolic disorders by activating the ire1a-xbp1 pathway in zebrafish liver

Zhang, Ying; Jiao, Yaqi; Tao, Yue; Li, Zixu; Yu, Hui; Han, Siyue; Yang, Yang

doi:10.1016/j.jhazmat.2021.125243

Cited by 24 publications

(7 citation statements)

References 53 publications

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“…It is worth noting that IRE-1α is extremely signi cant in the liver because hepatocytes are rich in both smooth and rough ER for massive protein synthesis and processing. Although several studies have linked IRE-1α-XBP1 signaling to apoptosis or autophagy [20,21], the mechanisms connecting its downstream molecules and other types of programmed cell death, such as necroptosis and pyroptosis, remain poorly understood.…”

Section: Introductionmentioning

confidence: 99%

WITHDRAWN: IRE-1α is a key switch of pyroptosis and necroptosis in mice by dominating Gasdermin D

Zeng

Zheng

et al. 2022

Preprint

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Necroptosis and pyroptosis are lytic and inflammatory types of programmed cell death that require the membrane destruction predominantly driven by the mixed lineage kinase domain-like (MLKL) and gasdermin D (GSDMD), respectively. However, the crosstalk between them remains largely unknown. Here, we disclose that inositol-requiring enzyme-1α (IRE-1α) is a potential modulator of both necroptosis and pyroptosis, particularly in liver pathology. In vivo, we found that pharmacological suppression of IRE-1α resulted in serious acute liver failure, which may be attributable to the downregulation of GSDMD and caspase-8 while remarkable upregulation of necroptosis markers receptor-interacting serine/threonine-protein kinase 1 (RIPK1), RIPK3 and MLKL. However, by using thapsigargin (THP) to moderately restore the IRE-1α level, liver failure was distinctly alleviated. Conversely, ER stressor tunicamycin (TM) promoted IRE-1α activity, which initiated liver pyroptosis by increasing GSDMD and NLRP3. But maintaining the IRE-1α balance by moderate inhibition of IRE-1α effectively improved mouse survival. In vitro, we demonstrated that inhibition of IRE-1α led to distinct necroptosis accompanied by the reduction of GSDMD in LO-2 cells and mouse primary hepatocytes. Nevertheless, by using lipopolysaccharide (LPS) to specifically inspire the GSDMD level, necroptosis was obvious ameliorated. In addition, overexpression of IRE-1α in LO-2 cells obviously increased pyroptotic markers, such as GSDMD and NLRP3, but downregulated the necroptosis markers p-MLKL and p-RIPK3. In conclusion, enhanced expression of IRE-1α triggers hepatic pyroptosis, while IRE-1α deficiency activates hepatic necroptosis, and both processes are closed related to the activity of GSDMD in mice. So, IRE-1α may be a promising therapeutic target in tissue injuries.

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Section: Introductionmentioning

confidence: 99%

WITHDRAWN: IRE-1α is a key switch of pyroptosis and necroptosis in mice by dominating Gasdermin D

Zeng

Zheng

et al. 2022

Preprint

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“…They can either activate the downstream estrogen signaling (Lee et al, 2014 ) or stimulate AhR and downstream signaling (Hsieh et al, 2012 ). Adult exposure to phthalates is also reported to cause estrogen receptor stress and autophagy in zebrafish liver through activation of the IRE-XBP1 pathway (Zhang et al, 2021 ).…”

Section: Determining Common Mechanisms Associated With Exposure To Edcsmentioning

confidence: 99%

Developmental Exposure to Endocrine Disrupting Chemicals and Its Impact on Cardio-Metabolic-Renal Health

et al. 2021

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Developmental origin of health and disease postulates that the footprints of early life exposure are followed as an endowment of risk for adult diseases. Epidemiological and experimental evidence suggest that an adverse fetal environment can affect the health of offspring throughout their lifetime. Exposure to endocrine disrupting chemicals (EDCs) during fetal development can affect the hormone system homeostasis, resulting in a broad spectrum of adverse health outcomes. In the present review, we have described the effect of prenatal EDCs exposure on cardio-metabolic-renal health, using the available epidemiological and experimental evidence. We also discuss the potential mechanisms of their action, which include epigenetic changes, hormonal imprinting, loss of energy homeostasis, and metabolic perturbations. The effect of prenatal EDCs exposure on cardio-metabolic-renal health, which is a complex condition of an altered biological landscape, can be further examined in the case of other environmental stressors with a similar mode of action.

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“…By contrast, traditional Chinese formulas composed of multiple herbs act on complex diseases through multiple targets, pathways and biological processes as a suitable strategy for alleviating T2DM. Previous studies have demonstrated that suppression of ER stress and excessive autophagy may protect β-cells from damage in the HG model [33]. In this study, we used spontaneous type 2 diabetic db/db mice, a classical T2DM animal model, since this model develops diabetes spontaneously without need for additional interventions or synthetic agents [34].…”

Section: Jttf Protects Against Hg-induced β-Cell Injurymentioning

confidence: 99%

Jiedu Tongluo Tiaogan Formula Protects Pancreatic Islet Cells Against Dysfunction by Relieving Endoplasmic Reticulum Stress and Excessive Autophagy via Regulating CaMKKβ/AMPK Pathway

Piao

Jin

et al. 2021

Preprint

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Background: Endoplasmic reticulum stress (ERS) and excessive autophagy are increasingly recognized as risk factors associated with development and progression of β-cell dysfunction. Jiedu Tongluo Tiaogan Formula (JTTF) has known anti-glucotoxicity activities, but its pharmacological effects on pancreatic cell are not clearly understood. This study was designed to investigate JTTF effects/mechanisms on in vitro glucotoxicity (HG)-induced ERS and excessive autophagic damage of pancreatic cells in vitro and on in vivo pancreatic injury in db/db mice. Methods: The chemical composition of a JTTF preparation were analyzed using high-performance liquid chromatographic fingerprinting. Meanwhile, cell viability, glucose-stimulated insulin secretion, insulin biosynthesis dysfunction, Ca2+ overload, ERS and excessive autophagy were assessed in JTTF-pretreated pancreatic β-cells with HG-induced injury. Hematoxylin and eosin staining and immunohistochemical analyses of pancreatic tissues revealed effects of in vivo JTTF pretreatment on development of HG-induced pancreatic injury in db/db mice. Results: Five JTTF chemical components were identified. Our results revealed that JTTF treatment protected β-cells from HG injury by increasing insulin biosynthesis and glucose-stimulated insulin secretion (GSIS), while also decreasing Ca2+ overload, ERS and excessive autophagy. Furthermore, protective effects of JTTF treatment against HG-induced β-cell ERS and excessive autophagy were linked to regulation of CaMKKβ/AMPK pathway functions, while JTTF administration as confirmed to reverse pancreatic injury in db/db mice. Conclusions: Collectively, the results presented here indicate that JTTF may prevent islet cell dysfunction in T2DM mice by inhibiting CaMKKβ/AMPK pathway-mediated ERS and excessive autophagy. These findings enhance our understanding of mechanisms underlying beneficial JTTF-induced amelioration of T2DM.

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Monobutyl phthalate can induce autophagy and metabolic disorders by activating the ire1a-xbp1 pathway in zebrafish liver

Cited by 24 publications

References 53 publications

WITHDRAWN: IRE-1α is a key switch of pyroptosis and necroptosis in mice by dominating Gasdermin D

WITHDRAWN: IRE-1α is a key switch of pyroptosis and necroptosis in mice by dominating Gasdermin D

Developmental Exposure to Endocrine Disrupting Chemicals and Its Impact on Cardio-Metabolic-Renal Health

Jiedu Tongluo Tiaogan Formula Protects Pancreatic Islet Cells Against Dysfunction by Relieving Endoplasmic Reticulum Stress and Excessive Autophagy via Regulating CaMKKβ/AMPK Pathway

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