Protective effect of secretory APE1/Ref‐1 on doxorubicin‐induced cardiotoxicity via suppression of ROS and p53 pathway

ESC Heart Failure, Journal Year: 2024, Volume and Issue: 11(2), P. 1182 - 1193

Published: Jan. 29, 2024

Abstract Aims The clinical application of doxorubicin (DOX), a potent anthracycline anticancer drug that effectively treats various malignancies, is limited by its side effects, such as cardiomyopathy. Apurinic/apyrimidinic endonuclease 1/redox factor‐1 (APE1/Ref‐1) multifunctional protein can be secreted and promising target for the reduction DOX‐induced inflammation oxidative stress. We aimed to investigate protective role secretory APE1/Ref‐1 against cardiac injury. Methods results Designated adenoviral preprotrypsin‐leading sequence (Ad‐PPTLS‐APE1/Ref‐1) was used overexpress assess in preventing cardiomyopathy vitro . Our findings revealed exposure significantly decreased N‐terminal pro‐B‐type natriuretic peptide levels DOX‐treated H9C2 cells. In addition, reduced severity cardiomyocyte injury apoptosis both vivo cardiotoxicity models. observed cardioprotective effects were mediated via inhibition p53 signalling pathway enhancement cell viability through attenuation stress cardiomyocytes. Conclusions study provides evidence has potential inhibit toxicity inhibiting related These suggest supplementation strategy attenuate damage preclinical model. Further investigations are essential validate therapeutic efficacy safety intervention human subjects.

Language: Английский

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The role of HDAC2 inhibition in cardioprotection against doxorubicin-induced myocardial injury

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 26, 2025

The molecular mechanisms underlying cardioprotection against doxorubicin (DOX)-induced myocardial injury are poorly understood. Histone deacetylase 2 (HDAC2) plays a significant role in oxidative stress, apoptosis, and mitochondrial dysfunction is implicated many human diseases, This study investigated the relationship between HDAC2 expression DOX-induced using vivo rat model of cardiotoxicity vitro experiments with H9c2 cardiomyocytes. was established by administering DOX via intraperitoneal injections. suppressed rats sodium butyrate (SB) Echocardiography measurements were performed at baseline on day 15 post-treatment. euthanized cardiac tissues harvested. tissue samples analyzed hematoxylin eosin H&E staining, immunohistochemistry, Masson Sirius Red TUNEL western blotting to determine status apoptosis. In experiments, cells treated DOX. or transfected shRNA knockdown (shHDAC2). from different groups Rt-qPCR, CCK-8 cell viability assay, cardiomyocyte treatment induced rats. DOX-treated showed significantly higher levels compared corresponding controls. However, inhibition mitigated suggested strong association injury. cells, shHDAC2 alleviated apoptosis enhacing AKT phosphorylation. These findings demonstrated that silencing protected activating PI3K/AKT signaling pathway. Suppressing Therefore, promising therapeutic target for mitigating

Language: Английский

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APEX1 attenuates ERS-induced paraptosis by inhibiting the P53 pathway in LECs

Experimental Eye Research, Journal Year: 2025, Volume and Issue: unknown, P. 110393 - 110393

Published: April 1, 2025

Language: Английский

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Sulfiredoxin 1 ameliorates doxorubicin-induced cardiotoxicity by suppressing oxidative stress and inflammation via the Sirt1/NLRP3 pathway

International Immunopharmacology, Journal Year: 2024, Volume and Issue: 141, P. 113010 - 113010

Published: Aug. 24, 2024

Language: Английский

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Role of APE1 in hepatocellular carcinoma and its prospects as a target in clinical settings (Review)

Molecular and Clinical Oncology, Journal Year: 2024, Volume and Issue: 21(5)

Published: Sept. 6, 2024

In recent years, the incidence of liver cancer has increased annually. However, current medical treatments for are limited, and most patients have a high risk recurrence after surgery. Therefore, discovery development novel treatment targets is urgently needed. Apurinic/apyrimidinic endonuclease 1 (APE1) protein that DNA repair function serves an important role in various physiological processes, including reduction-oxidation, cell proliferation differentiation. The expression levels APE1 abnormally elevated cells, as ectopic gene been reported, addition to other abnormal signs, such migration. it could be suggested indicator hepatocellular carcinogenesis. may used therapeutic target tumors proposed targeted therapy against potentially inhibit progression tumors. present review aimed introduce processes tumor cells feasibility using potential target, providing direction clinical cancer.

Language: Английский

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