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PRDX6 alleviated heart failure by inhibiting doxorubicin-induced ferroptosis through the JAK2/STAT1 pathway inactivation

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Abstract

Peroxiredoxin 6 (PRDX6) is a protective biomarker associated with ferroptosis in heart failure (HF). This study investigated the specific mechanism of PRDX6 on doxorubicin (DOX)–induced ferroptosis in HF. Wistar rats and H9c2 cells were induced by DOX to construct HF models. Pathological changes and collagen deposition in myocardium were investigated using HE and Masson staining. PRDX6 levels, indexes of ferroptosis, and JAK2/STAT1 pathway were detected by qRT-PCR, Western blot, and biochemical kits. DOX promoted heart weight/body weight, increased inflammation and collagen deposition, increased PTGS2 and MDA levels, and decreased SLC7A11, GPX4, FTH1, and PRDX6 levels in myocardium. PRDX6 overexpression reduced PTGS2, MDA, Fe2+, and LDH levels, inhibited JAK2 and STAT1 phosphorylation, and increased SLC7A11, GPX4, and FTH1 levels in DOX-added H9c2 cells. RO8191 and erastin reversed the inhibition of PRDX6 on ferroptosis through the JAK2/STAT1 pathway. Overall, PRDX6 alleviated HF by inhibiting DOX-induced ferroptosis through the JAK2/STAT1 pathway inactivation.

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Data availability

All data can be obtained from the corresponding author.

Abbreviations

HF :

Heart failure

PRDX6 :

Peroxiredoxin 6

Sp1 :

Specificity protein 1

LPS :

Lipopolysaccharide

HE :

Hematoxylin-eosin

DMEM :

Dulbecco’s modified Eagle’s medium

FBS :

Fetal bovine serum

CCK-8 :

Cell counting kit-8

qRT-PCR :

Quantitative real-time polymerase chain reaction

MDA :

Malondialdehyde

OD :

Optical density

RIPA :

Radioimmunoprecipitation assay

SD :

Standard deviation

ANOVA :

Analysis of variance

ROS :

Reactive oxygen species

DOX :

Doxorubicin

PTGS2 :

Prostaglandin-endoperoxide synthase 2

GPX4 :

Glutathione peroxidase 4

SLC7A11 :

Solute carrier family 7 member

FTH1 :

Ferritin heavy chain 1

LDH :

Lactate dehydrogenase

SDS-PAGE :

Sodium dodecyl sulfate–polyacrylamide gel electrophoresis

NC :

Nitrocellulose

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Authors and Affiliations

  1. Department of Cardiology, Jiujiang First People’s Hospital, Jiujiang, 332000, Jiangxi, China

    Jie Xiong

  2. Department of Internal Medicine, Affiliated Hospital of Jiujiang University, Jiujiang, 332000, Jiangxi, China

    Rong Zhou

  3. Department of Cardiology, the Third Xiangya Hospital, Central South University, Changsha, 410013, Hunan, China

    Xu Deng

Authors
  1. Jie Xiong
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  2. Rong Zhou
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  3. Xu Deng
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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by J. X. and R. Z. The first draft of the manuscript was written by X. D. and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Xu Deng.

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Ethics approval

The animal study was reviewed and approved by the Animal Ethical Committee of Jiujiang First People’s Hospital (No. JJSDYRMYY-YXLL-2023-192).

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The authors declare no competing interests.

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Xiong, J., Zhou, R. & Deng, X. PRDX6 alleviated heart failure by inhibiting doxorubicin-induced ferroptosis through the JAK2/STAT1 pathway inactivation. In Vitro Cell.Dev.Biol.-Animal (2024). https://doi.org/10.1007/s11626-024-00889-0

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