Peroxiredoxin 6 overexpression regulates adriamycin-induced myocardial injury, oxidative stress and immune response in rats

Guo, Jianshu; Cao, Weiping; Chen, Chi; Chen, Xiaohan

doi:10.21037/atm-20-6598

Cited by 6 publications

(4 citation statements)

References 25 publications

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“…On the other hand, upon LPS treatment, PRDX6 knock-down cells showed increased NF-κB-dependent expression of pro-inflammatory cytokines such as TNF-α, IL1-α, IL1-β, or IL-8 [ 108 ]. Furthermore, PRDX6 overexpression alleviated adriamycine-induced myocardial injury in rats and decreased expression of IL1-β and IL-6 [ 109 ]. Collectively, these studies reported rather contradictory findings, suggesting the association of PRDX6 with cytokine expression might be context-dependent and probably related to its different enzymatic activities and cellular localization of PRDX6.…”

Section: Discussionmentioning

confidence: 99%

Peroxiredoxin 6 protects irradiated cells from oxidative stress and shapes their senescence-associated cytokine landscape

et al. 2022

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Cellular senescence is a complex stress response defined as an essentially irreversible cell cycle arrest mediated by the inhibition of cell cycle-specific cyclin dependent kinases. The imbalance in redox homeostasis and oxidative stress have been repeatedly observed as one of the hallmarks of the senescent phenotype. However, a large-scale study investigating protein oxidation and redox signaling in senescent cells in vitro has been lacking. Here we applied a proteome-wide analysis using SILAC-iodoTMT workflow to quantitatively estimate the level of protein sulfhydryl oxidation and proteome level changes in ionizing radiation-induced senescence (IRIS) in hTERT-RPE-1 cells. We observed that senescent cells mobilized the antioxidant system to buffer the increased oxidation stress. Among the antioxidant proteins with increased relative abundance in IRIS, a unique 1-Cys peroxiredoxin family member, peroxiredoxin 6 (PRDX6), was identified as an important contributor to protection against oxidative stress. PRDX6 silencing increased ROS production in senescent cells, decreased their resistance to oxidative stress-induced cell death, and impaired their viability. Subsequent SILAC-iodoTMT and secretome analysis after PRDX6 silencing showed the downregulation of PRDX6 in IRIS affected protein secretory pathways, decreased expression of extracellular matrix proteins, and led to unexpected attenuation of senescence-associated secretory phenotype (SASP). The latter was exemplified by decreased secretion of pro-inflammatory cytokine IL-6 which was also confirmed after treatment with an inhibitor of PRDX6 iPLA2 activity, MJ33. In conclusion, by combining different methodological approaches we discovered a novel role of PRDX6 in senescent cell viability and SASP development. Our results suggest PRDX6 could have a potential as a drug target for senolytic or senomodulatory therapy.

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Section: Discussionmentioning

confidence: 99%

Peroxiredoxin 6 protects irradiated cells from oxidative stress and shapes their senescence-associated cytokine landscape

et al. 2022

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“…A study in mice found that Peroxiredoxin 1 can prevent cardiac hypertrophy and HF caused by pressure overload by activating Nrf2/HO-1 signaling (Tang et al 2020). Two recent basic studies on cardiovascular diseases have found that Peroxiredoxin 6 overexpression regulates doxorubicin-induced myocardial injury in rats (Guo et al 2020). Overexpression of PRDX6 can prevent Ang II-induced inflammation and endothelial dysfunction in human umbilical vein endothelial cells (Li et al 2020).…”

Section: Discussionmentioning

confidence: 99%

Integrated bioinformatics and machine learning strategies reveal PRDX6 as the key ferroptosis-associated molecular biosignature of heart failure

Jiang¹,

Jiang²

2022

gpb

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Heart failure (HF) is the leading cause of death and public health problems in the global population. This study aimed to identify and validate ferroptosis-related biomarkers associated with HF in clinical medicine using bioinformatics and machine learning strategies. Weighted co-expression network analysis (WGCNA) was applied to screen the module genes and analyze their biological functions and pathways. Ferroptosis-associated genes (FAG) in HF were determined and then machine learning algorithms were used for screening. Next, multiple external independent microarrays were used to verify molecular biosignature. Simultaneously, CIBERSORT was applied to estimate the immune infiltration landscape. Combined with the results of the WGCNA, 25 FAGs were determined and 6 FAMBs were selected by machine learning strategies. In addition, Peroxiredoxin 6 (PRDX6) was finally selected as the key ferroptosis-associated molecular biological feature based on multiple verifications of independent data sets. From the results of the infiltration and enrichment analysis, we believed that PRDX6, as a protective biomarker related to ferroptosis in HF, may help provide new ideas in the immunotherapy of HF.

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“…Apart from the immunosuppressive effect of DOX, the inflammatory response evoked by DOX with pro-inflammatory cytokine release has been interestingly linked to toxic effects of DOX, especially to the life-threatening cardiomyopathy, as well as liver and kidney injury [ 2 , 10 , 11 ]. Therefore, understanding DOX-induced inflammatory-immune response is essential for proper management of the toxic side effects observed during treatment especially on heart [ 12 , 13 ].…”

Section: Introductionmentioning

confidence: 99%

Quercetin Alleviates the Immunotoxic Impact Mediated by Oxidative Stress and Inflammation Induced by Doxorubicin Exposure in Rats

et al. 2021

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Doxorubicin (DOX) is a chemotherapeutic agent against hematogenous and solid tumors with undesirable side effects including immunosuppression. Quercetin (QUR), a natural flavonoid abundant in fruits and vegetables, has a potent antioxidant activity. The aim of the current study was to assess the impact of QUR on DOX-induced hematological and immunological dysfunctions in a rodent model. Randomly grouped rats were treated as follows: control, QUR alone (50 mg/kg for 15 days per os), DOX alone (2.5 mg/kg I/P, three times a week, for two weeks), and co-treated rats with QUR for 15 days prior to and concomitantly with DOX (for two weeks), at the doses intended for groups two and three. DOX alone significantly disrupted the erythrogram and leukogram variables. Serum immunoglobulin (IgG, IgM, and IgE) levels and the activities of catalase (CAT) and superoxide dismutase (SOD) in spleen were declined. The DNA damage traits in spleen were elevated with an upregulation of the expression of the apoptotic markers (p53 and Caspase-3 genes) and the proinflammatory cytokines (IL-6 and TNF-α genes), while the expression of CAT gene was downregulated. These biochemical changes were accompanied by morphological changes in the spleen of DOX-treated rats. Co-treatment with QUR abated most of the DOX-mediated alterations in hematological variables, serum immunoglobulins, and spleen antioxidant status, pro-inflammatory and apoptotic responses, and histopathological alterations. In essence, these data suggest that QUR alleviated DOX-induced toxicities on the bone marrow, spleen, and antibody-producing cells. Supplementation of chemotherapy patients with QUR could circumvent the DOX-induced inflammation and immunotoxicity, and thus prevent chemotherapy failure.

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Peroxiredoxin 6 overexpression regulates adriamycin-induced myocardial injury, oxidative stress and immune response in rats

Cited by 6 publications

References 25 publications

Peroxiredoxin 6 protects irradiated cells from oxidative stress and shapes their senescence-associated cytokine landscape

Peroxiredoxin 6 protects irradiated cells from oxidative stress and shapes their senescence-associated cytokine landscape

Integrated bioinformatics and machine learning strategies reveal PRDX6 as the key ferroptosis-associated molecular biosignature of heart failure

Quercetin Alleviates the Immunotoxic Impact Mediated by Oxidative Stress and Inflammation Induced by Doxorubicin Exposure in Rats

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