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

IF 16.4 1区化学 Q1 CHEMISTRY, MULTIDISCIPLINARY

Accounts of Chemical Research Pub Date : 2024-04-01 Epub Date: 2024-03-26 DOI:10.1007/s11626-024-00889-0

Jie Xiong, Rong Zhou, Xu Deng

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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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PRDX6 通过抑制 JAK2/STAT1 通路的失活来抑制多柔比星诱导的铁氧化，从而缓解心力衰竭。

过氧化物歧化酶 6 (PRDX6) 是一种与心力衰竭（HF）中铁细胞减少相关的保护性生物标志物。本研究探讨了PRDX6对多柔比星（DOX）诱导的心力衰竭铁细胞减少的具体机制。通过 DOX 诱导 Wistar 大鼠和 H9c2 细胞构建 HF 模型。使用 HE 和 Masson 染色法检测心肌的病理变化和胶原沉积。通过 qRT-PCR、Western 印迹和生化试剂盒检测了 PRDX6 水平、铁变态反应指数和 JAK2/STAT1 通路。DOX促进了心脏重量/体重，增加了炎症和胶原沉积，提高了PTGS2和MDA水平，降低了心肌中SLC7A11、GPX4、FTH1和PRDX6的水平。在添加了 DOX 的 H9c2 细胞中，PRDX6 的过表达降低了 PTGS2、MDA、Fe2+ 和 LDH 水平，抑制了 JAK2 和 STAT1 磷酸化，提高了 SLC7A11、GPX4 和 FTH1 水平。RO8191 和厄拉斯汀逆转了 PRDX6 通过 JAK2/STAT1 通路对铁突变的抑制作用。总之，PRDX6通过抑制JAK2/STAT1通路的失活来抑制DOX诱导的铁卟啉沉着，从而缓解了HF。

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来源期刊

Accounts of Chemical Research 化学-化学综合

CiteScore

31.40

自引率

1.10%

发文量

312

审稿时长

2 months

期刊介绍： Accounts of Chemical Research presents short, concise and critical articles offering easy-to-read overviews of basic research and applications in all areas of chemistry and biochemistry. These short reviews focus on research from the author’s own laboratory and are designed to teach the reader about a research project. In addition, Accounts of Chemical Research publishes commentaries that give an informed opinion on a current research problem. Special Issues online are devoted to a single topic of unusual activity and significance. Accounts of Chemical Research replaces the traditional article abstract with an article "Conspectus." These entries synopsize the research affording the reader a closer look at the content and significance of an article. Through this provision of a more detailed description of the article contents, the Conspectus enhances the article's discoverability by search engines and the exposure for the research.