Peroxiredoxin 3 deficiency accelerates chronic kidney injury in mice through interactions between macrophages and tubular epithelial cells

Hwang, Inah; Uddin, Jamal; Lee, Gayoung; Jiang, Songling; Pak, Eun Seon; Ha, Hunjoo

doi:10.1016/j.freeradbiomed.2018.12.002

Cited by 24 publications

(18 citation statements)

References 49 publications

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“…Mitochondrial oxidative stress and intracellular inflammation are generally associated with APAP toxicity ( 2 , 3 , 25 , 28 , 39 ). To assess the protective effect of the PRX family members on APAP hepatotoxicity, specific siRNAs for three mitochondria-associated PRXs (PRX3, PRX5 and PRX6) ( 25 , 40 ) were transfected into hepatocytes prior to APAP-induced cytotoxicity ( Figures S1A–C ).…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have shown that PRX3-knockout mice accumulate relatively high intracellular ROS levels, which increases the severity of LPS-induced lung injury ( 27 ). Moreover, PRX3 deficiency accelerates chronic kidney disease by promoting fibrosis and inflammation accompanied by mitochondrial oxidative stress ( 28 ). In contrast, PRX3 overexpression in mice protects against traumatic neuronal injury by preserving mitochondrial function and mitochondrial biogenesis ( 29 ) and prevents mitochondrial oxidative damage induced by intestinal ischemia/reperfusion (I/R) injury ( 30 ).…”

Section: Introductionmentioning

confidence: 99%

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Peroxiredoxin 3 Inhibits Acetaminophen-Induced Liver Pyroptosis Through the Regulation of Mitochondrial ROS

et al. 2021

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Pyroptosis is a newly discovered form of cell death. Peroxiredoxin 3 (PRX3) plays a crucial role in scavenging reactive oxygen species (ROS), but its hepatoprotective capacity in acetaminophen (APAP)-induced liver disease remains unclear. The aim of this study was to assess the role of PRX3 in the regulation of pyroptosis during APAP-mediated hepatotoxicity. We demonstrated that pyroptosis occurs in APAP-induced liver injury accompanied by intense oxidative stress and inflammation, and liver specific PRX3 silencing aggravated the initiation of pyroptosis and liver injury after APAP intervention. Notably, excessive mitochondrial ROS (mtROS) was observed to trigger pyroptosis by activating the NLRP3 inflammasome, which was ameliorated by Mito-TEMPO treatment, indicating that the anti-pyroptotic role of PRX3 relies on its powerful ability to regulate mtROS. Overall, PRX3 regulates NLRP3-dependent pyroptosis in APAP-induced liver injury by targeting mitochondrial oxidative stress.

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Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Peroxiredoxin 3 Inhibits Acetaminophen-Induced Liver Pyroptosis Through the Regulation of Mitochondrial ROS

et al. 2021

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“…ROS loosen the cerebral vasculature by decreasing the tight junction proteins and activating matrix metalloproteinases (MMPs) in endothelial cells, resulting in the disruption of the blood-brain barrier (BBB) which causes the infiltration of circulating immune cells and inflammatory factors into the brain [5]. Oxidative stress also induces the production of inflammatory cytokines in macrophages [6].…”

Section: Introductionmentioning

confidence: 99%

Cerebral sterile inflammation in neurodegenerative diseases

Otani

Shichita

2020

Inflamm Regener

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Therapeutic strategies for regulating neuroinflammation are expected in the development of novel therapeutic agents to prevent the progression of central nervous system (CNS) pathologies. An understanding of the detailed molecular and cellular mechanisms of neuroinflammation in each CNS disease is necessary for the development of therapeutics. Since the brain is a sterile organ, neuroinflammation in Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS) is triggered by cerebral cellular damage or the abnormal accumulation of inflammatogenic molecules in CNS tissue through the activation of innate and acquired immunity. Inflammation and CNS pathologies worsen each other through various cellular and molecular mechanisms, such as oxidative stress or the accumulation of inflammatogenic molecules induced in the damaged CNS tissue. In this review, we summarize the recent evidence regarding sterile immune responses in neurodegenerative diseases.

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“…However, as mentioned above, experimental evidence suggests that PRDX1 can perform exceptional antioxidant functions in comparison with other peroxiredoxins. Indeed, while genetic knock-outs of other peroxiredoxins do not significantly hamper the survival of the animals and cause relatively mild defects [16][17][18][19][20], Prdx1-deficient mice suffer from shortened survival due to development of hemolytic anemia and multiple tumors, including mammary carcinomas [20]. The role of PRDX1 during the development of breast cancer is, however, complex.…”

Section: Introductionmentioning

confidence: 99%

Triple Combination of Ascorbate, Menadione and the Inhibition of Peroxiredoxin-1 Produces Synergistic Cytotoxic Effects in Triple-Negative Breast Cancer Cells

et al. 2020

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Triple-negative breast cancer (TNBC) is an aggressive form of mammary malignancy currently without satisfactory systemic treatment options. Agents generating reactive oxygen species (ROS), such as ascorbate (Asc) and menadione (Men), especially applied in combination, have been proposed as an alternative anticancer modality. However, their effectiveness can be hampered by the cytoprotective effects of elevated antioxidant enzymes (e.g., peroxiredoxins, PRDX) in cancer. In this study, PRDX1 mRNA and protein expression were assessed in TNBC tissues by analysis of the online RNA-seq datasets and immunohistochemical staining of tissue microarray, respectively. We demonstrated that PRDX1 mRNA expression was markedly elevated in primary TNBC tumors as compared to non-malignant controls, with PRDX1 protein staining intensity correlating with favorable survival parameters. Subsequently, PRDX1 functionality in TNBC cell lines or non-malignant mammary cells was targeted by genetic silencing or chemically by auranofin (AUR). The PRDX1-knockdown or AUR treatment resulted in inhibition of the growth of TNBC cells in vitro. These cytotoxic effects were further synergistically potentiated by the incubation with a combination of the prooxidant agents, Asc and Men. In conclusion, we report that the PRDX1-related antioxidant system is essential for maintaining redox homeostasis in TNBC cells and can be an attractive therapeutic target in combination with ROS-generating agents.

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Peroxiredoxin 3 deficiency accelerates chronic kidney injury in mice through interactions between macrophages and tubular epithelial cells

Cited by 24 publications

References 49 publications

Peroxiredoxin 3 Inhibits Acetaminophen-Induced Liver Pyroptosis Through the Regulation of Mitochondrial ROS

Peroxiredoxin 3 Inhibits Acetaminophen-Induced Liver Pyroptosis Through the Regulation of Mitochondrial ROS

Cerebral sterile inflammation in neurodegenerative diseases

Triple Combination of Ascorbate, Menadione and the Inhibition of Peroxiredoxin-1 Produces Synergistic Cytotoxic Effects in Triple-Negative Breast Cancer Cells

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